CN105496979B - A kind of Rasagiline tablet - Google Patents
A kind of Rasagiline tablet Download PDFInfo
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- CN105496979B CN105496979B CN201610037015.4A CN201610037015A CN105496979B CN 105496979 B CN105496979 B CN 105496979B CN 201610037015 A CN201610037015 A CN 201610037015A CN 105496979 B CN105496979 B CN 105496979B
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- hydroxypropyl methylcellulose
- microcrystalline cellulose
- rasagiline
- solution
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
Abstract
The invention discloses a kind of Rasagiline, which includes：Contain by weight percentage：1%~3% rasagiline mesilate, 1.5%~3% hydroxypropyl methylcellulose, 0.3%~3% EDTA 2Na, 50%~75% microcrystalline cellulose, the tablet is prepared using wet granulation, including main ingredient and EDTA 2Na are dissolved in the hydroxypropyl methylcellulose solution of part, the suspension that the solution is formed with portions microcrystalline cellulose is stirred, mixed again with remaining microcrystalline cellulose and remaining hydroxypropyl methylcellulose solution carry out wet granulation, tabletting and obtain.Prescription of the present invention is simple, each process is easily operated, and production cost is low, is suitble to industrialized production；And obtained product has good long-time stability.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of Rasagiline tablet.
Background technology
Parkinson's disease (PD) is also known as shaking plasy, is second largest nerve degenerative diseases after Alzheimer after being ill.Pa
The morbidity of the gloomy disease of gold mainly due to dopaminergic neuron progressive denaturation in brain nigro-striatal system, causes line shape
In the main movement region of body caused by the exhaustion of neurotransmitter dopamine.Its two big characteristic pathological mark --- substantia nigra of midbrain
The presence of Lewy corpusculums in a large amount of dead and remaining neurons of dopaminergic neuron selectivity of compact part is the root of clinical symptoms
Where source, important physiological foundation is since dopamine is reduced and acetylcholine loses with respect between central neurotransmitter caused by increasing
Weighing apparatus.The cause of disease of Parkinson's disease may relate to age ageing, genetic and environmental factor etc..
The drug for the treatment of Parkinson's disease has levodopa, DA receptor stimulating agents, MAO-B inhibitor, COMT inhibitor at present.
Levodopa is the main force for treating Parkinson's disease always since the 1960s, although levodopa has it not replace
Superiority, but be merely possible to the precursor of DA to supplement DA contents, be susceptible to serious complication.Compared with left-handed more
Bar, Rasagiline has better security, can improve movement and cognitive function, can be individually used for Early Parkinson's disease patient
Treatment.
The chemical name of Rasagiline：(1R) -2,3- dihydro-N-2- propinyl -1H- indenes -1- amine, individually can effectively treat morning
Phase Parkinson's disease, better tolerance, length of holding time can slow down this sick progress in the medication of Parkinson's disease early stage.Lei Shaji
When blue and levodopa shares, significantly shorten the time of "Off" state, and show good tolerance.
EP0436492 discloses application of the Rasagiline in treatment Parkinson's disease, memory disorders etc. disease, discloses thunder
Sha Jilan is played a role with the administration of the dosage forms such as oral solid formulation, liquid preparation, emulsifiable paste, preparation capable of permeating skin.
CN101152153 discloses a kind of medicinal composition of oral administration solid, the methanesulfonic acid containing 0.5%~3% parts by weight
Rasagiline, not less than 40% and less than the pentabasis alcohol of 60% parts by weight and/or having for hexahydroxylic alcohols and 0.5%~3% parts by weight
Machine acid.Contain more pentabasis alcohol and/or hexahydroxylic alcohols in the invention, including mannitol, xylitol, sorbierite, maltitol, though
The product of the right invention has preferable stability, but its cost is higher.
CN102333442 discloses a kind of delayed release rasagiline formulation, by mixing Rasagiline, citric acid and/or apple
Tartaric acid prepares core with pharmaceutically acceptable auxiliary material, and then core cladding is got up using acidproof coating.The invention needs thunder is husky
Ji Lan is prepared into medicine core, then recycles acid resisting material coating, complex production process, process control is stringent, adds industry
Change the difficulty produced greatly.
CN103315983 discloses a kind of rasagiline formulations and preparation method thereof, containing the stabilizer as acidulant,
Acidulant includes the buffering pair of organic monoacid and its conjugate base composition and the buffering of organic monoacid and strong base-weak acid salt composition
It is right.The invention solves the stability problem of product by adding in acidulant, so as to which prescription is complicated, production cost is higher.
Rasagiline tablet played an important role in terms of Parkinson's disease is treated.But the quality of said preparation still exists
Problem, pharmaceutical industry are carrying out the research and development Rasagiline novel formulation for improving the quality of the pharmaceutical preparations always.
In disclosed various prior arts, some prescriptions are complicated, and some production processes are more, and process control is stringent,
Some costs are higher, it is necessary to be further improved the formulation and technology of the product, it is made to be more suitable for industrialized production.The present inventor
During the product development, by largely studying, have surprisingly found that, can be produced using specific adhesive and technique
The rasagiline mesilate tablet of stable quality.
The content of the invention
The object of the present invention is to provide a kind of Rasagiline tablet, which has prescription simple, easily operated, is produced into
The advantages of this is low, is easy to industrialized production, and long-time stability are good.
The present inventor, by a large amount of contrast tests, has found following prescription and technological factor in the research of Rasagiline tablet
Have an impact to the stability of the Rasagiline tablet：Adhesive selection hydroxypropyl methylcellulose, EDTA-2Na, microcrystalline cellulose,
In, adhesive and microcrystalline cellulose are segmented addition during tablet producing technology, and main ingredient Rasagiline is first dissolved in adhesive
Solution, then mixed with the suspension that portions microcrystalline cellulose is formed, add filler, disintegrant and microcrystalline cellulose and bonding
Agent solution mixing granulation.The combination of these prescriptions and technological factor obtains stable Rasagiline tablet.
In one embodiment, Rasagiline tablet of the invention, comprising：Rasagiline mesilate 1%~3%, hydroxypropyl
Methylcellulose 1.5%~3%, EDTA-2Na0.1%~3%, microcrystalline cellulose 50%~75%, surplus are medicinal auxiliary for other
Material, by weight percentage, other described pharmaceutic adjuvants include filler, disintegrant and lubricant, and the tablet is by following
Method is made, and this method includes procedure below：
(1) take portions microcrystalline cellulose water-dispersible into hydroxypropyl methylcellulose solution hydroxypropyl methylcellulose water dissolution
Form microcrystalline cellulose suspension；
(2) part hydroxypropyl methylcellulose solution dissolving Rasagiline and EDTA-2Na are taken, adds microcrystalline cellulose suspension
Liquid stirs to get mixed liquor；
(3) after mixing filler, disintegrant and remaining microcrystalline cellulose with the mixed liquor of upper step, add remaining
Hydroxypropyl methylcellulose solution carries out wet granulation；
(4) by particle made from upper step and mix lubricant tabletting.
Preferably, Rasagiline tablet of the invention, the filler is selected from starch, pre-paying starch and lactose, described
Lubricant, dosage account for the 0.8%~3% of piece weight, and the lubricant is selected from stearic acid, talcum powder and superfine silica gel powder, described to collapse
Agent is solved, dosage accounts for the 2%~8% of piece weight, and the disintegrant is selected from carboxyrnethyl starch sodium, crospovidone and crosslinking carboxylic first fiber
Plain sodium.
Preferably, Rasagiline tablet of the invention, the part microcrystalline cellulose of step (1) account for the 3%~7% of piece weight,
The concentration of hydroxypropyl methylcellulose solution in step (1) is 5-10%, the part hydroxypropyl methylcellulose in step (1)
Solution accounts for the 30-35% of hydroxypropyl methylcellulose total solution weight.
Preferably, Rasagiline tablet of the invention, the weight percent of EDTA-2Na is 0.5%~1.5%, and crystallite is fine
The weight percent of dimension element is 50%~65%, and the weight percent of lubricant is 0.8%~3%, and lubricant is preferably tristearin
Acid, superfine silica gel powder, the weight percent of disintegrant is 2%~8%, is preferably 3%~5%, disintegrant is preferably carboxymethylstarch
Sodium, the dosage of filler are the 8-38% of tablet formulation amount, are preferably starch.
The preparation method of the Rasagiline piece of the present invention, using this field belong to the various steps of wet granulation and condition into
Row, such as fast Speed mixer, wave extruding granulation, fluidized-bed spray granulation.The key of the preparation method of the present invention is：Main ingredient
Rasagiline is dissolved in EDTA-2Na in the hydroxypropyl methylcellulose solution of part, which forms mixed with portions microcrystalline cellulose
Suspension is stirred, and wet granulation is carried out with the mixed liquor and remaining microcrystalline cellulose and hydroxypropyl methylcellulose solution.
Further, hydroxypropyl methylcellulose solution water is prepared.After preparing, a part of solution is taken, adds in first sulphur
Sour Rasagiline and EDTA-2Na, stirring and dissolving.The microcrystalline cellulose of recipe quantity 3%~7% is taken, it is water-dispersible.It will be husky added with thunder
Ji Lan is mixed with the binder solution of EDTA-2Na with the suspension containing portions microcrystalline cellulose, is dispersed with stirring, mixing time
30 minutes or more, preferably 30 minutes to 60 minutes.Suspension temperature should be maintained at 30 DEG C to 40 DEG C when being dispersed with stirring, this can
With by simply heat or the natural type of cooling realize.The amount of taking of hydroxypropyl methylcellulose solution and preparation microcrystalline cellulose
The water of plain suspension to be sufficient to allow mixed mixed liquor, can be completely used for wet granulation, to avoid with dilutional hyponatremia
Main ingredient Rasagiline is caused to lose, therefore, the water those skilled in the art for preparing microcrystalline cellulose suspension can be with routine
Knowledge determines.
The advantages of tablet of the present invention and good effect：
1. the tablet stability of the present invention is very good, when key is to pelletize, portions microcrystalline cellulose is mixed in prescription
Suspension needs are stirred and mix with main ingredient Rasagiline, EDTA-2Na and hydroxypropyl methylcellulose solution, so as to solve tablet
Stability problem.By test of many times, this hair people has found EDTA-2Na, hydroxypropyl methylcellulose to improving rasagiline formulations
Stability has a certain effect, but this is for solving the stability of the product not enough.Microcrystalline cellulose is as a kind of common
Solid pharmaceutical preparation filler in the production of solid pharmaceutical preparation, is added in generally as solid form.In the development process of this product,
Found by a large number of experiments, main ingredient Rasagiline and EDTA-2Na be dissolved in the hydroxypropyl methylcellulose solution of part, then with containing
The suspension for having portions microcrystalline cellulose is stirred, and is obtained containing main ingredient Rasagiline, EDTA-2Na, part hypromellose
Element, the mixed liquor of portions microcrystalline cellulose.The mixed liquor as the adhesive used first all with remaining microcrystalline cellulose,
Other fillers and disintegrant mixing, add remaining hydroxypropyl methylcellulose solution, then wet granulation routinely carries out
Granulation.In the preparation process of the tablet of the present invention, and not all microcrystalline cellulose all adds in solid form,
Part is added in the form of suspension, and need to be stirred with main ingredient Rasagiline, EDTA-2Na, hydroxypropyl methylcellulose mixed
It closes.This is different from the change of routine operation, can make the tablet of the present invention have good long-time stability.
2. for the tablet of the present invention using conventional wet lay granulating process, easy to operate, process is easily controllable, is more suitable for industrializing
Production.
3. the tablet of the present invention is using common, conventional pharmaceutic adjuvant, predominantly microcrystalline cellulose, other filler bags
Include starch, pre-paying starch, lactose.These are all cheap pharmaceutic adjuvants, and therefore, the present invention has cost advantage.
Specific embodiment
The following examples are of the invention substantive for illustrating and understanding, the scope of but do not limit the invention in any way.
The amount of the rasagiline mesilate used in following embodiment is based on Rasagiline, 1.56mg rasagiline mesilates
It is approximately equivalent to 1mg Rasagilines.
Embodiment 1：Piece weight 100mg
Prescription：
| Supplementary material title | Weight percent % |
| Rasagiline mesilate | 1.56 |
| Hydroxypropyl methylcellulose | 2 |
| Carboxyrnethyl starch sodium | 8 |
| EDTA-2Na | 0.1 |
| Microcrystalline cellulose | 50 |
| Starch | 37.54 |
| Stearic acid | 0.4 |
| Superfine silica gel powder | 0.4 |
| It is total | 100 |
Technique：
1. prepare binder solution：5% hydroxypropyl methylcellulose solution is prepared, takes about 30% amount, adds in EDTA-2Na, first
Sulfonic acid Rasagiline, stirring and dissolving.The microcrystalline cellulose of recipe quantity 5% is taken, it is water-dispersible.It will be added with the viscous of main ingredient and EDTA-2Na
Mixture solution is mixed with microcrystalline cellulose suspension, and mixeding liquid temperature is controlled to be dispersed with stirring 30 minutes for 30 DEG C to 40 DEG C.
2. surplus microcrystalline cellulose, carboxyrnethyl starch sodium, starch are uniformly mixed, first with the mixed solution of step 1, then with residue
Hydroxypropyl methylcellulose solution, carry out wet granulation.Wet granular is dry, whole grain.
3. add in stearic acid, superfine silica gel powder tabletting after mixing.
Embodiment 2：Piece weight 156mg
(difference lies in the microcrystalline cellulose addition form of recipe quantity 3% is different from comparative example 1)
Prescription：
| Supplementary material title | Percentage % |
| Rasagiline mesilate | 1 |
| Hydroxypropyl methylcellulose | 2.5 |
| Crospovidone | 2 |
| EDTA-2Na | 0.5 |
| Microcrystalline cellulose | 60 |
| Pre-paying starch | 32 |
| Stearic acid | 1 |
| Talcum powder | 1 |
| It is total | 100 |
Technique：
1. prepare binder solution：8% hydroxypropyl methylcellulose solution is prepared, takes about 35% amount, adds in EDTA-2Na, first
Sulfonic acid Rasagiline, stirring and dissolving.The microcrystalline cellulose of recipe quantity 3% is taken, it is water-dispersible.It will be added with the viscous of main ingredient and EDTA-2Na
Mixture solution is mixed with microcrystalline cellulose suspension, and mixeding liquid temperature is controlled to be dispersed with stirring 60 minutes for 30 DEG C to 40 DEG C.
2. surplus microcrystalline cellulose, crospovidone, pre-paying starch are uniformly mixed, first with the mixed solution of step 1, then
With remaining hydroxypropyl methylcellulose solution, wet granulation is carried out.Wet granular is dry, whole grain.
3. add in stearic acid, talcum powder tabletting after mixing.
Embodiment 3：Piece weight 78mg
Prescription：
| Supplementary material title | Percentage % |
| Rasagiline mesilate | 2 |
| Hydroxypropyl methylcellulose | 1.5 |
| Cross-linked carboxymethyl cellulose sodium | 3 |
| EDTA-2Na | 1.5 |
| Microcrystalline cellulose | 65 |
| Lactose | 25.2 |
| Talcum powder | 1 |
| Superfine silica gel powder | 0.8 |
| It is total | 100 |
Technique：
1. prepare binder solution：10% hydroxypropyl methylcellulose solution is prepared, takes about 25% amount, addition EDTA-2Na,
Rasagiline mesilate, stirring and dissolving.The microcrystalline cellulose of recipe quantity 7% is taken, it is water-dispersible.It will be added with main ingredient and EDTA-2Na
Binder solution is mixed with microcrystalline cellulose suspension, and mixeding liquid temperature is controlled to be dispersed with stirring 40 minutes for 30 DEG C to 40 DEG C.
2. surplus microcrystalline cellulose, cross-linked carboxymethyl cellulose sodium, lactose are uniformly mixed, first with the mixed solution of step 1, then
With remaining hydroxypropyl methylcellulose solution, wet granulation is carried out.Wet granular is dry, whole grain.
3. add in talcum powder, superfine silica gel powder tabletting after mixing.
Embodiment 4：Piece weight 52mg
Prescription：
Technique：
1. prepare binder solution：8% hydroxypropyl methylcellulose solution is prepared, takes about 30% amount, adds in EDTA-2Na, first
Sulfonic acid Rasagiline, stirring and dissolving.The microcrystalline cellulose of recipe quantity 4% is taken, it is water-dispersible.It will be added with the viscous of main ingredient and EDTA-2Na
Mixture solution is mixed with microcrystalline cellulose suspension, and mixeding liquid temperature is controlled to be dispersed with stirring 50 minutes for 30 DEG C to 40 DEG C.
2. surplus microcrystalline cellulose, carboxyrnethyl starch sodium, starch are uniformly mixed, first with the mixed solution of step 1, then with residue
Hydroxypropyl methylcellulose solution, carry out wet granulation.Wet granular is dry, whole grain.
3. add in sliding stearic acid tabletting after mixing.
Comparative example 1：Piece weight 156mg
Prescription：
| Supplementary material title | Percentage % |
| Rasagiline mesilate | 1 |
| Hydroxypropyl methylcellulose | 2.5 |
| Crospovidone | 2 |
| EDTA-2Na | 0.5 |
| Microcrystalline cellulose | 60 |
| Pre-paying starch | 32 |
| Stearic acid | 1 |
| Talcum powder | 1 |
| It is total | 100 |
Technique：
1. prepare binder solution：8% hydroxypropyl methylcellulose solution is prepared, takes about 35% amount, adds in EDTA-2Na, first
Sulfonic acid Rasagiline, stirring and dissolving are spare.
2. microcrystalline cellulose, crospovidone, pre-paying starch are uniformly mixed, first using the binder solution of step 1, then
With remaining hydroxypropyl methylcellulose solution, wet granulation is carried out.Wet granular is dry, whole grain.
3. add in stearic acid, talcum powder tabletting after mixing.
Comparative example 2：Piece weight 78mg
Prescription：
| Supplementary material title | Percentage % |
| Rasagiline mesilate | 2 |
| Hydroxypropyl methylcellulose | 1.5 |
| Cross-linked carboxymethyl cellulose sodium | 3 |
| EDTA-2Na | 1.5 |
| Microcrystalline cellulose | 65 |
| Lactose | 25.2 |
| Talcum powder | 1 |
| Superfine silica gel powder | 0.8 |
| It is total | 100 |
Technique：
1. prepare binder solution：10% hydroxypropyl methylcellulose solution is prepared, takes about 25% amount, addition EDTA-2Na,
Rasagiline mesilate, stirring and dissolving are spare.
2. microcrystalline cellulose, cross-linked carboxymethyl cellulose sodium, lactose are uniformly mixed, first with the binder solution of step 1, then use
Remaining hydroxypropyl methylcellulose solution carries out wet granulation.Wet granular is dry, whole grain.
3. add in talcum powder, superfine silica gel powder tabletting after mixing.
Comparative example embodiment 3
Hydroxypropyl methylcellulose in 1 prescription of embodiment is substituted with povidone, other prescriptions and technique are constant.
Comparative example embodiment 4
Microcrystalline cellulose in 1 prescription of embodiment is substituted with lactose, other prescriptions and technique are constant.
Experimental example
Accelerated stability is investigated
Sample use is common aluminum-plastic packaged, under conditions of 40 ± 2 DEG C of temperature, relative humidity RH75% ± 5%, is added
Fast study on the stability.Result of the test shows during investigation, the Rasagiline that comparative example 1 and comparative example 2 produce
Piece, S- isomers, single impurity, total impurities have certain growth, and the result is shown in Tables 1 and 2s；, the thunder that produces of comparative example 3 it is husky
Content 0.21,0.26,0.35 of the S- isomers, single impurity, total impurities of lucky orchid piece at 6th month.Comparative example 4 produces
Rasagiline piece content 0.25,0.31,0.38 at 6th month of S- isomers, single impurity, total impurities.Present invention system
The tablet of standby Rasagiline piece, that is, 1~embodiment of embodiment 4, indices are stablized without significant change, product quality, the result is shown in
Table 3-6.
1 comparative example of table, 1 accelerated stability investigates result：
2 comparative example of table, 2 accelerated stability investigates result：
3 embodiment of table, 1 accelerated stability investigates result：
4 embodiment of table, 2 accelerated stability investigates result：
5 embodiment of table, 3 accelerated stability investigates result：
6 embodiment of table, 4 accelerated stability investigates result：
Long-time stability investigate result：
Sample use is common aluminum-plastic packaged, under conditions of 25 ± 2 DEG C of temperature, relative humidity RH60% ± 10%, carries out
Long-time stability are investigated.The result shows that during investigation, the Rasagiline piece of the invention prepared, indices become without apparent
Change, product quality is stablized.
7 embodiment of table, 1 long-time stability investigate result：
8 embodiment of table, 2 long-time stability investigate result：
9 embodiment of table, 3 long-time stability investigate result：
10 embodiment of table, 4 long-time stability investigate result：
With upper table 1-10's the result shows that, Rasagiline tablet of the invention, due to use hydroxypropyl methylcellulose for bonding
Agent and microcrystalline cellulose, and the technique added in using segmentation, Rasagiline dissolve in binder solution in advance, the tablet of acquisition is very
Stablize, impurity is few, and quality is good.And what the unused prescription for adopting hydroxypropyl methylcellulose and microcrystalline cellulose and not use segmentation added in
The Rasagiline tablet that technique obtains stores rear impurity content and increases for a long time, and stability is poor.
Make simple variation in the spirit of the present invention and the appropriate increase and decrease of auxiliary material falls within the model of the present invention
It encloses.
Claims (1)
1. a kind of Rasagiline tablet, comprising：1~3% rasagiline mesilate, 1.5~3% hydroxypropyl methylcellulose, 0.1
~3% EDTA-2Na, 50~75% microcrystalline cellulose, surplus is other pharmaceutic adjuvants, by weight percentage, described
Other pharmaceutic adjuvants include filler, disintegrant and lubricant, and the tablet is made by following methods, and this method includes following mistake
Journey：
(1) hydroxypropyl methylcellulose water dissolution is taken into part hydroxypropyl methylcellulose solution dissolving thunder into hydroxypropyl methylcellulose solution
Sha Jilan and EDTA-2Na, adds portions microcrystalline cellulose, stirs to get mixed liquor；
(2) after mixing filler, disintegrant and remaining microcrystalline cellulose with the mixed liquor of upper step, it is remaining to add step
Hydroxypropyl methylcellulose solution carries out wet granulation；
(3) by particle obtained and mix lubricant tabletting；
Wherein, the filler is selected from starch, pregelatinized starch and lactose, and dosage accounts for the 8%~38% of piece weight, described to collapse
It solves agent and is selected from carboxyrnethyl starch sodium, crospovidone and cross-linked carboxymethyl cellulose sodium, dosage accounts for the 2~8% of piece weight, the lubrication
Agent is selected from stearic acid, talcum powder and superfine silica gel powder, and dosage accounts for the 0.8~3% of piece weight,
The part microcrystalline cellulose of step (1) accounts for the 3~7% of piece weight,
The concentration of hydroxypropyl methylcellulose solution in step (1) is 5-10%,
Part hydroxypropyl methylcellulose solution in step (1) accounts for the 30-35% of hydroxypropyl methylcellulose total solution weight.
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| CN201610037015.4A CN105496979B (en) | 2015-12-08 | 2016-01-20 | A kind of Rasagiline tablet |
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| CN2015109036361 | 2015-12-08 | ||
| CN201610037015.4A CN105496979B (en) | 2015-12-08 | 2016-01-20 | A kind of Rasagiline tablet |
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| CN107753446B (en) * | 2017-03-07 | 2021-02-19 | 常州市第四制药厂有限公司 | Rasagiline tablet and preparation method thereof |
| CN114469902A (en) | 2020-10-23 | 2022-05-13 | 上海上药中西制药有限公司 | Sublingual film agent of rasagiline or pharmaceutical salt thereof, preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102048717A (en) * | 2009-10-29 | 2011-05-11 | 重庆医药工业研究院有限责任公司 | Stable rasagiline composition |
| EP2389927A1 (en) * | 2010-05-30 | 2011-11-30 | Abdi Ibrahim Ilac Sanayi ve Ticaret Anonim Sirketi | Pharmaceutical formulations of rasagiline |
| CN103315983A (en) * | 2012-12-20 | 2013-09-25 | 上海中西制药有限公司 | Rasagiline preparation and preparation method thereof |
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| WO2015086768A1 (en) * | 2013-12-11 | 2015-06-18 | Krka, D.D., Novo Mesto | Pharmaceutical composition comprising a pharmaceutically acceptable salt of rasagiline |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102048717A (en) * | 2009-10-29 | 2011-05-11 | 重庆医药工业研究院有限责任公司 | Stable rasagiline composition |
| EP2389927A1 (en) * | 2010-05-30 | 2011-11-30 | Abdi Ibrahim Ilac Sanayi ve Ticaret Anonim Sirketi | Pharmaceutical formulations of rasagiline |
| CN103315983A (en) * | 2012-12-20 | 2013-09-25 | 上海中西制药有限公司 | Rasagiline preparation and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 新型抗帕金森病药——雷沙吉兰;刘廷辉;《中国药学杂志》;20060630;第41卷(第11期);参见全文 * |
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