CN115400090A - Orally disintegrating tablet composition of rasagiline and preparation method thereof - Google Patents
Orally disintegrating tablet composition of rasagiline and preparation method thereof Download PDFInfo
- Publication number
- CN115400090A CN115400090A CN202211226301.7A CN202211226301A CN115400090A CN 115400090 A CN115400090 A CN 115400090A CN 202211226301 A CN202211226301 A CN 202211226301A CN 115400090 A CN115400090 A CN 115400090A
- Authority
- CN
- China
- Prior art keywords
- acid
- orally disintegrating
- rasagiline
- disintegrating tablet
- tablet composition
- 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.)
- Pending
Links
Classifications
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- 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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- 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
-
- 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
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Psychology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses an orally disintegrating tablet composition of rasagiline or a medicinal salt thereof, which comprises the following components in parts by weight: 1-4% of rasagiline, 55-80% of a filler, 10-35% of a disintegrant, 1-5% of an acidic stabilizer, 1-2% of a glidant, 1-2% of a lubricant, and 0.5-2% of a sweetener; the disintegrant comprises two disintegrants which are free of metal ions; the two metal ion-free disintegrants are selected from the combination of crospovidone and low-substituted hydroxypropyl cellulose or the combination of crospovidone and pregelatinized starch, and the acid stabilizer is preferably the combination of citric acid and malic acid. The rasagiline orally disintegrating tablet composition has good stability, the disintegration time is within 1min, the requirements of Chinese pharmacopoeia on orally disintegrating tablets are met, no gravel feeling or insoluble auxiliary material feeling exists in oral cavities, and the rasagiline orally disintegrating tablet composition is simple in preparation process and free of special equipment requirements.
Description
Technical Field
The invention relates to the technical field of medicines, and in particular relates to an orally disintegrating tablet composition of rasagiline and a preparation method thereof.
Background
Dysphagia in parkinson's disease is a manifestation of swallowing dysfunction. Aspiration pneumonia caused by swallowing dysfunction is an important and common cause of hospitalization of parkinson patients, possibly leading to serious complications and even death. The orally disintegrating tablet is a preparation formulation specially designed for improving compliance, has fast disintegration speed and fast absorption, does not need drinking water after taking the tablet, and is most suitable for the old and bedridden patients.
Rasagiline is a monoamine oxidase-B inhibitor, has a chemical name of (1R) -2,3-dihydro-N-2-propynyl-1H-indene-1-amine, is clinically used for treating Parkinson, can inhibit the decomposition of neurotransmitter dopamine, and has an action mechanism mainly comprising promotion of dopamine release of a dopamine pre-synaptic membrane, inhibition of degradation of released dopamine and inhibition of dopamine reabsorption by the pre-synaptic membrane.
Publication No. CN113730363A discloses a preparation method of rasagiline mesylate orally disintegrating tablets, which comprises the steps of preparing drug-loaded pellets from raw material drugs of rasagiline mesylate, a filling agent and an adhesive, coating the pellets with an enteric coating solution, finally uniformly mixing the coated pellets with a disintegrating agent, a flavoring agent and a lubricating agent to obtain a total mixed material, and tabletting. The orally disintegrating tablet of rasagiline or its medicinal salt prepared by the method has good stability, and can be used for actual pharmaceutical industrial production. However, the preparation method has complex process, uses various auxiliary materials and process equipment, has long time consumption in the preparation process and high production cost, and the enteric coating of the pellets needs certain operation experience of production personnel.
Publication No. CN103494766a discloses a rasagiline mesylate orally disintegrating tablet pharmaceutical composition, which comprises rasagiline or a pharmaceutically acceptable salt of rasagiline, and particles having a non-filamentous microstructure of at least two sugar alcohols. The sorbitol and xylitol used in the composition are easy to absorb moisture and agglomerate, the fluidity is poor, the preparation process of the preparation needs strict moisture control, and the disintegration time limit during the stability period is obviously prolonged.
The publication number CN101874790A discloses a rasagiline orally disintegrating tablet and a preparation method thereof, the rasagiline or the orally disintegrating tablet of the pharmaceutical salt thereof comprises the following components in percentage by weight: 0.25-2% of rasagiline or medicinal salt thereof, 85-91% of spray-dried mannitol, 3-10% of disintegrant, 0.5-2% of glidant, 0.5-2% of lubricant, 0-2% of sweetener and 0-2% of flavoring agent, wherein the adopted disintegrant is a combined disintegrant of croscarmellose sodium and sodium carboxymethyl starch or crospovidone and sodium carboxymethyl starch. The orally disintegrating tablet of rasagiline or the pharmaceutical salt of rasagiline has enough hardness, can meet the requirements of production and packaging, has good taste and shorter disintegration time, but the used disintegrating agents contain metal ions, and the impurity growth in the stability period exceeds the limit.
The invention develops the rasagiline orally disintegrating tablet composition with simple preparation process, proper taste and good stability on the basis of the traditional rasagiline tablet.
Disclosure of Invention
The invention aims to provide an orally disintegrating tablet composition of rasagiline or a medicinal salt of rasagiline and a preparation method thereof. The rasagiline orally disintegrating tablet composition provided by the invention is simple in preparation process and good in stability.
In order to realize the purpose of the invention, the technical scheme of the invention is as follows:
in one aspect, the present invention provides an orally disintegrating tablet composition of rasagiline or a pharmaceutically acceptable salt thereof, comprising the following components in parts by weight: 1-4% rasagiline, 55-80% of a filler, 10-35% of a disintegrant, 1-5% of an acidic stabilizer, 1-2% of a glidant, 1-2% of a lubricant, 0.5-2% of a sweetener;
the disintegrating agent comprises two disintegrating agents without metal ions;
the two metal ion-free disintegrants are selected from crospovidone and low-substituted hydroxypropyl cellulose combination, or the combination of the crospovidone and pregelatinized starch;
preferably, the mass ratio of crospovidone to low-substituted hydroxypropyl cellulose in the two metal ion-free disintegrants is 1: (0.01-3);
further preferably, the mass ratio of the crospovidone to the low-substituted hydroxypropyl cellulose is 1: (0.01-2);
most preferably, the mass ratio of the crospovidone to the low-substituted hydroxypropyl cellulose is 1: (0.1-2).
Preferably, the crospovidone accounts for 1-15% of the mass of the orally disintegrating tablet composition;
further preferably, the crospovidone accounts for 10-15% by mass of the orally disintegrating tablet composition.
Preferably, the mass ratio of crospovidone to pregelatinized starch in the two metal ion-free disintegrants is 1: (0.01-3);
further preferably, the mass ratio of the crospovidone to the pregelatinized starch is 1: (0.01-2);
most preferably, the mass ratio of crospovidone to pregelatinized starch is 1: (0.1-2).
Preferably, the acidic stabilizer is at least one selected from malic acid, acetic acid, tartaric acid, citric acid, fumaric acid, maleic acid, lactic acid, sorbic acid, propionic acid, succinic acid, salicylic acid, oxalic acid, benzenesulfonic acid, cysteine hydrochloride, L-aspartic acid and glutamic acid.
Further preferably, the acidic stabilizer is at least one selected from malic acid, acetic acid, tartaric acid and citric acid.
Further preferably, the acidic stabilizer is at least one selected from malic acid and citric acid.
Most preferably, the acidic stabilizer is a combination of malic acid and citric acid.
Still more preferably, the mass ratio of malic acid to citric acid in the acidic stabilizer is 1: (0.02-1);
still further preferably, the mass ratio of malic acid to citric acid in the acidic stabilizer is 1: (0.03-1);
most preferably, the mass ratio of malic acid to citric acid in the acidic stabilizer is 1: (0.3-1).
Preferably, the malic acid accounts for 0.1-5% of the mass ratio of the orally disintegrating tablet composition;
further preferably, the malic acid accounts for 0.3-3% by mass of the orally disintegrating tablet composition.
Preferably, the orally disintegrating tablet composition comprises rasagiline: disintegrating agent: the mass ratio of the acidic stabilizer is 1: (1-60): (0.2-10).
Further preferably, the weight ratio of rasagiline: disintegrating agent: the mass ratio of the acidic stabilizer is 1: (1-45): (0.2-6).
Most preferably, the orally disintegrating tablet composition comprises rasagiline: disintegrating agent: the mass ratio of the acidic stabilizer is 1: (5-40): (1-5).
Specifically, the rasagiline medicinal salt refers to a pharmaceutically acceptable salt, and comprises a salt formed by inorganic acid such as phosphoric acid, hydrochloric acid and sulfuric acid, and a salt formed by organic acid such as citric acid and tartaric acid, and the rasagiline medicinal salt comprises rasagiline mesylate, rasagiline citrate, rasagiline malate and rasagiline tartrate.
Specifically, the chemical name of the crospovidone is crospolyvinylpyrrolidone (pvpp), and the molecular formula is (C) 6 H 9 NO)n。
Specifically, the CAS number of the low-substituted hydroxypropyl cellulose is 78214-41-2.
Specifically, the CAS number of the pregelatinized starch is 9005-25-8, and the molecular formula is (C) 6 H 10 O 5 )n。
In particular, the crosslinked polyvinylpyrrolidoneThe molecular formula of the ketone is (C) 6 H 9 NO) n, CAS number 25249-54-1.
Specifically, the molecular formula of the carboxypropyl starch is CHO. X, and the CAS number is 9049-76-7.
Further preferably, the filler is at least one selected from lactose, mannitol, corn starch, ethyl cellulose, magnesium oxide, magnesium carbonate, sucrose, calcium carbonate, and microcrystalline cellulose.
Still more preferably, the filler is selected from at least one of lactose, mannitol, corn starch, microcrystalline cellulose.
Further preferably, the glidant is selected from at least one of silicon dioxide and aerosil.
Further preferably, the lubricant is at least one selected from magnesium stearate, sodium fumarate stearate, talc, calcium stearate and polyethylene glycol.
Still more preferably, the lubricant is selected from at least one of magnesium stearate, sodium fumarate stearate, talc.
Further preferably, the sweetener is selected from at least one of sucralose, acesulfame potassium, aspartame, neotame, steviosin, sodium saccharin, steviol glycosides.
Still more preferably, the sweetener is selected from at least one of aspartame, acesulfame potassium, saccharin sodium and sucralose.
In another aspect, the present invention provides a process for the preparation of an orally disintegrating tablet composition of rasagiline or a pharmaceutically acceptable salt thereof, comprising:
the powder direct-pressing process comprises mixing the above materials by equivalent progressive method, and tabletting to obtain tablet core with hardness of 40-110N;
preferably, the hardness of the tablet core is 50-90N;
further preferably, the tablet core hardness is 50-70N.
Specifically, the powder direct compression process refers to a method for directly tabletting a mixture of the composition and pharmaceutically acceptable auxiliary materials without granulation.
Specifically, the operation steps of the equal incremental method are that firstly, a small amount of components are taken, an equal amount of large components are added, then, large components with the same amount as the mixture are taken and uniformly mixed, and the amount is increased by the times until all the components are uniformly mixed.
The invention has the beneficial effects that:
(1) The orally disintegrating tablet composition of rasagiline of the present invention has good stability and no gritty sensation or insoluble adjuvant sensation in the oral cavity.
(2) The orally disintegrating tablet composition of rasagiline has simple preparation process and no special equipment requirement.
Detailed Description
The following non-limiting examples are presented to enable those of ordinary skill in the art to more fully understand the present invention and are not intended to limit the invention in any way. The following is merely an exemplary illustration of the scope of the invention as claimed, and various changes and modifications of the invention of the present application may be made by those skilled in the art based on the disclosure, which also fall within the scope of the invention as claimed.
The present invention will be further described below by way of specific examples. The various chemicals used in the examples of the present invention were obtained by conventional commercial routes unless otherwise specified. Hereinafter, the contents are mass contents.
In some embodiments of the invention, the crospovidone has an average particle size of 100 μm; the content of the substituent of the low-substituted hydroxypropyl cellulose is 12 percent; the pregelatinized starch contains 5% of free amylose, 15% of free amylopectin and 80% of unmodified starch.
The preparation method of the orally disintegrating tablet composition of rasagiline comprises the following steps:
(1) Mixing rasagiline and disintegrant, adding filler, glidant and sweetener in equal amount by step, and mixing;
(2) Sieving the mixture obtained in step (1);
(3) Finally adding the lubricant and continuously mixing;
(4) Tabletting to obtain the final product.
Example 1
The formulation of the orally disintegrating tablet composition of rasagiline is specifically shown in the following table 1:
TABLE 1
| Components | %/tablet |
| Rasagiline | 1 |
| Mannitol | 65 |
| Cross-linked polyvidone | 15 |
| Low-substituted hydroxypropyl cellulose | 13.7 |
| Malic acid | 0.3 |
| Citric acid | 1 |
| Silicon dioxide | 1.5 |
| Magnesium stearate | 1 |
| Aspartame | 1.5 |
Example 2
The formulation of the orally disintegrating tablet composition of rasagiline is specified in table 2 below:
TABLE 2
| Components | %/tablet |
| Rasagiline | 2 |
| Lactose | 72 |
| Cross-linked polyvidone | 10 |
| Low-substituted hydroxypropyl cellulose | 5 |
| Malic acid | 2.5 |
| Citric acid | 2.5 |
| Silica gel micropowder | 2 |
| Stearic acid fumaric acid sodium salt | 2 |
| Acesulfame potassium | 2 |
Example 3
The formulation of the orally disintegrating tablet composition of rasagiline is specified in table 3 below:
TABLE 3
| Components | %/tablet |
| Rasagiline | 4 |
| Corn starch | 59.5 |
| Cross-linked polyvidone | 12 |
| Low-substituted hydroxypropyl cellulose | 19.7 |
| Malic acid | 0.3 |
| Citric acid | 1 |
| Silicon dioxide | 1.5 |
| Talcum powder | 1.5 |
| Sucralose | 0.5 |
Example 4
Example 4 is different from example 3 (the best example) in that the disintegrant in example 4 is crospovidone and pregelatinized starch, and the rest is the same.
Comparative example 1
The difference from example 3 (the best example) is that the disintegrant in the orally disintegrating tablet composition of rasagiline is specifically crospovidone and croscarmellose sodium, without acid stabilizer, and the rest is the same.
Comparative example 2
The difference from example 3 (the best example) is that 2 disintegrants of rasagiline orally disintegrating tablet composition do not contain metal ions, specifically crospovidone and low substituted hydroxypropylcellulose, no acid stabilizer, and the rest are the same.
Comparative example 3
The difference from example 3 (the best example) is that the disintegrant in the orally disintegrating tablet composition of rasagiline is crospovidone and sodium carboxymethyl starch, the rest being the same.
Comparative example 4
The difference from example 3 (the best example) is that the mass ratio of crospovidone to low-substituted hydroxypropylcellulose in the orally disintegrating tablet composition of rasagiline is 3:10, the rest being the same.
Comparative example 5
The difference from example 3 (the best example) is that the mass ratio of malic acid to citric acid in the acidic stabilizer in the orally disintegrating tablet composition of rasagiline is 1:2, the rest are the same.
Comparative example 6
Best example from example 3) is that the ratio of rasagiline: disintegrating agent: the mass ratio of the acidic stabilizer is 1:0.25:4, the rest are the same.
EXAMPLE 5 detection of orally disintegrating tablet compositions of rasagiline
The impurity detection method comprises the following steps:
the related substance detection method adopts high performance liquid chromatography (0512 of the four-part general regulation in 2020 edition of Chinese pharmacopoeia), and octadecylsilane chemically bonded silica is used as a filling agent; perchloric acid buffer (ph 2.5) -acetonitrile (80) as mobile phase; the detection wavelength was 210nm.
The orally disintegrating tablet compositions of rasagiline prepared in examples 1-4 and comparative examples 1-6 were used for impurity detection, and the results are shown in table 4 below:
TABLE 4
The method for detecting the disintegration time limit comprises the following steps:
disintegration time limit inspection method (0921, the four-part general rule of the 2020 edition of Chinese pharmacopoeia) oral disintegration tablet inspection method device, wherein about 900mL of water with the temperature of 37 +/-1 ℃ is contained in a 1000mL beaker, and the water level is adjusted so that a screen mesh is 15 +/-1 mm below the water surface when the stainless steel tube is at the lowest position. The instrument was started, the sample was placed in a stainless steel tube while timing, and the time for the sample to completely disintegrate and pass through the screen was recorded. The assay was performed 6 times in parallel and the mean value was taken.
The orally disintegrating tablet compositions of rasagiline prepared in examples 1-4 and comparative examples 1-6 were subjected to disintegration time limit test, and the test results are shown in table 5 below:
TABLE 5
| Sample (I) | Disintegration time limit |
| Example 1 | 30s |
| Example 2 | 30s |
| Example 3 | 45s |
| Example 4 | 42s |
| Comparative example 1 | 1min |
| Comparative example 2 | 1min30s |
| Comparative example 3 | 1min20s |
| Comparative example 4 | 2min |
| Comparative example 5 | 1min |
| Comparative example 6 | 5min |
Results of the experiment
As can be seen from the test data in Table 4 above, examples 1-4 of the present invention provide orally disintegrating tablet compositions of rasagiline having lower levels of known and unknown impurities and shorter disintegration times. In comparative examples 1-2, the combination of the disintegrant is changed into the combination of crospovidone and sodium croscarmellose or the combination of crospovidone and low-substituted hydroxypropyl cellulose, and when no acid stabilizer is added into the disintegrant, the impurities are obviously increased, and the disintegration time is obviously prolonged compared with that of examples 1-4. In comparative example 3, only when the combination of the disintegrant was changed to crospovidone and sodium carboxymethyl starch, the influence on impurities was large, the total impurity content reached 1.18%, and the disintegration time was long. When the mass ratio of crospovidone to low-substituted hydroxypropylcellulose is changed to 3 in comparative example 4, although the impurity content of comparative example 4 is the same as that of example 2, the results in table 5 show that the disintegration time of comparative example 4 is 2min, the disintegration time of example 2 is 30s, and the requirement of "chinese pharmacopoeia" on the disintegration time of orally disintegrating tablets within 1min is not satisfied in comparative example 4. In comparative example 5 only the mass ratio of malic acid to citric acid in the acidic stabilizer was changed, in comparative example 6 only rasagiline in the orally disintegrating tablet composition was changed: disintegrating agent: the results of the mass ratio of the acidic stabilizer show that the comparative examples 5 to 6 all significantly increase the content of impurities and increase the disintegration time, compared to examples 1 to 4.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the present invention, and any modifications, equivalents, improvements and the like made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. An orally disintegrating tablet composition of rasagiline or a pharmaceutically acceptable salt thereof, comprising the following components in parts by weight: 1-4% of rasagiline, 55-80% of a filler, 10-35% of a disintegrant, 1-5% of an acidic stabilizer, 1-2% of a glidant, 1-2% of a lubricant, and 0.5-2% of a sweetener;
the disintegrant comprises two disintegrants which are free of metal ions;
the two disintegrants not containing metal ions are selected from the combination of crospovidone and low-substituted hydroxypropyl cellulose, or the combination of the crospovidone and pregelatinized starch;
the acidic stabilizer is at least one selected from malic acid, acetic acid, tartaric acid, citric acid, fumaric acid, maleic acid, lactic acid, sorbic acid, propionic acid, succinic acid, salicylic acid, oxalic acid, benzenesulfonic acid, cysteine hydrochloride, L-aspartic acid and glutamic acid.
2. The orally disintegrating tablet composition according to claim 1, wherein the mass ratio of crospovidone to low substituted hydroxypropylcellulose in the two metal ion-free disintegrants is 1: (0.01-3).
3. The orally disintegrating tablet composition according to claim 2, wherein the mass ratio of crospovidone to low substituted hydroxypropylcellulose in the two metal ion-free disintegrants is 1: (0.01-2).
4. The orally disintegrating tablet composition according to claim 1, wherein the mass ratio of crospovidone to pregelatinized starch in the two metal ion-free disintegrants is 1: (0.01-3).
5. The orally disintegrating tablet composition according to claim 4, wherein the mass ratio of crospovidone to pregelatinized starch in the two metal ion-free disintegrants is 1: (0.01-2).
6. The orally disintegrating tablet composition of claim 1, wherein said acidic stabilizing agent is a combination of malic acid and citric acid.
7. The orally disintegrating tablet composition of claim 6, wherein the mass ratio of malic acid to citric acid in the acidic stabilizer is 1: (0.02-1).
8. The orally disintegrating tablet composition according to claim 1, wherein the ratio of rasagiline: disintegrating agent: the mass ratio of the acidic stabilizer is 1: (1-60): (0.2-10).
9. The orally disintegrating tablet composition of claim 8, wherein the ratio of rasagiline: disintegrating agent: the mass ratio of the acidic stabilizer is 1: (5-40): (1-5).
10. The process for the preparation of an orally disintegrating tablet composition according to any of claims 1 to 9, wherein the components are mixed by an equal incremental process using a powder direct compression process and compressed into tablets.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211226301.7A CN115400090A (en) | 2022-10-09 | 2022-10-09 | Orally disintegrating tablet composition of rasagiline and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211226301.7A CN115400090A (en) | 2022-10-09 | 2022-10-09 | Orally disintegrating tablet composition of rasagiline and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115400090A true CN115400090A (en) | 2022-11-29 |
Family
ID=84168377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211226301.7A Pending CN115400090A (en) | 2022-10-09 | 2022-10-09 | Orally disintegrating tablet composition of rasagiline and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115400090A (en) |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6126968A (en) * | 1995-09-20 | 2000-10-03 | Teva Pharmaceutical Industries, Ltd. | Stable compositions containing N-propargyl-1-aminoindan |
| CN1911211A (en) * | 2006-08-25 | 2007-02-14 | 重庆医药工业研究院有限责任公司 | Solid oral prepn. of leishajilan |
| CN101152153A (en) * | 2006-09-29 | 2008-04-02 | 北京德众万全药物技术开发有限公司 | Pharmaceutical composition containing rasagiline |
| US20100087768A1 (en) * | 2008-10-02 | 2010-04-08 | Forlano Paula | Transdermal drug delivery system for liquid active ingredient |
| CN102333442A (en) * | 2009-01-23 | 2012-01-25 | 泰华制药工业有限公司 | Delayed release rasagiline formulation |
| WO2013175493A1 (en) * | 2012-04-09 | 2013-11-28 | Cadila Healthcare Limited | Stable oral pharmaceutical compositions |
| WO2013182625A1 (en) * | 2012-06-08 | 2013-12-12 | Actavis Group Ptc Ehf | Pharmaceutical formulation with propargylamine compound |
| CN107095853A (en) * | 2017-04-01 | 2017-08-29 | 重庆康刻尔制药有限公司 | A kind of oral disnitegration tablet disintegrant combination and its application method |
| WO2022162612A1 (en) * | 2021-01-30 | 2022-08-04 | Intas Pharmaceuticals Ltd. | An orodispersible pharmaceutical solid dosage form of rasagiline |
-
2022
- 2022-10-09 CN CN202211226301.7A patent/CN115400090A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6126968A (en) * | 1995-09-20 | 2000-10-03 | Teva Pharmaceutical Industries, Ltd. | Stable compositions containing N-propargyl-1-aminoindan |
| CN1911211A (en) * | 2006-08-25 | 2007-02-14 | 重庆医药工业研究院有限责任公司 | Solid oral prepn. of leishajilan |
| CN101152153A (en) * | 2006-09-29 | 2008-04-02 | 北京德众万全药物技术开发有限公司 | Pharmaceutical composition containing rasagiline |
| US20100087768A1 (en) * | 2008-10-02 | 2010-04-08 | Forlano Paula | Transdermal drug delivery system for liquid active ingredient |
| CN102333442A (en) * | 2009-01-23 | 2012-01-25 | 泰华制药工业有限公司 | Delayed release rasagiline formulation |
| WO2013175493A1 (en) * | 2012-04-09 | 2013-11-28 | Cadila Healthcare Limited | Stable oral pharmaceutical compositions |
| WO2013182625A1 (en) * | 2012-06-08 | 2013-12-12 | Actavis Group Ptc Ehf | Pharmaceutical formulation with propargylamine compound |
| CN107095853A (en) * | 2017-04-01 | 2017-08-29 | 重庆康刻尔制药有限公司 | A kind of oral disnitegration tablet disintegrant combination and its application method |
| WO2022162612A1 (en) * | 2021-01-30 | 2022-08-04 | Intas Pharmaceuticals Ltd. | An orodispersible pharmaceutical solid dosage form of rasagiline |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4989733B2 (en) | Orally disintegrating tablets | |
| JP2012510483A5 (en) | ||
| WO2005055989A1 (en) | Drug-containing grains and solid preparation containing the grains | |
| JP2013505213A (en) | (Z) -2-Cyano-3-hydroxy-but-2-enoic acid- (4'-trifluoromethylphenyl) -amide tablet formulation with improved stability | |
| EP3188720B1 (en) | Tadalafil oral dispersible film and preparing method thereof | |
| JP6680297B2 (en) | Pharmaceutical composition for oral administration | |
| US20110060008A1 (en) | Pharmaceutical composition containing acetylcholine esterase inhibitor and method for the preparation thereof | |
| CN115400090A (en) | Orally disintegrating tablet composition of rasagiline and preparation method thereof | |
| JP4329947B1 (en) | Tablets for internal use | |
| CN110404079B (en) | Pharmaceutical composition of quinoline derivative or salt thereof containing no carbonate and low genotoxic impurity content | |
| JP2006316047A (en) | Pranlukast hydrate-containing preparation having relieved bitterness | |
| WO2011078827A1 (en) | The production method for effervescent tablet with cefdinir | |
| JP7355020B2 (en) | Pharmaceutical composition for oral administration | |
| US20060034911A1 (en) | New oral immediated release dosage form | |
| TW201113051A (en) | Oral disintegrating tablet and manufacturing method thereof | |
| TW200948398A (en) | Vancomycin hydrochloride tablet | |
| ES2694710T3 (en) | Tablets comprising an agent that masks the taste | |
| JP2020055776A (en) | Pharmaceutical composition containing memantine or pharmaceutically acceptable salt thereof and method for producing the same | |
| JP2019073488A (en) | Pharmaceutical tablets containing aprepitant as active ingredient | |
| JP5764688B2 (en) | Aripiprazole-containing orally disintegrating tablet and method for producing the same | |
| JP2019073445A (en) | Pharmaceutical composition containing aprepitant as active ingredient | |
| CN106880603A (en) | A kind of oral disnitegration tablet containing Topiroxostat and preparation method thereof | |
| JP2024004706A (en) | Pharmaceutical composition and pharmaceutical preparation | |
| JP2022135317A (en) | Linagliptin preparation | |
| EP2356984A1 (en) | Improved distigmine bromide formulation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |