CN109528665A - A kind of oral disintegrating tablet of drug and preparation method thereof for treating tardive dyskinesia - Google Patents
A kind of oral disintegrating tablet of drug and preparation method thereof for treating tardive dyskinesia Download PDFInfo
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- 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
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- 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
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Abstract
A kind of includes the oral disintegrating tablet of the pharmaceutically acceptable salt such as compound of formula I, the oral disintegrating tablet includes a effective amount of structure compound shown in formula I and pharmaceutically acceptable carrier, and the pharmaceutically acceptable carrier includes diluent, disintegrating agent, corrigent and lubricant.Oral disintegrating tablet disintegration rate provided by the invention is fast, and compliance is good, and bioavilability height is rapid-action, and simple production process.
Description
Technical field
The present invention relates to the field of pharmaceutical preparations of the VMAT-2 inhibitor of tardive dyskinesia.Relate more specifically to (S)-
2 amino -3- metliyl-butyric acid (2R, 3R, 11bR) -3- isobutyl group -9,10- dimethoxy -1,3,4,6,7,11b- hexahydro -2H- pyrroles
The oral disintegrating tablet of pharmaceutically acceptable salt and preparation method thereof of pyridine simultaneously [2,1-a] isoquinolin-2-yl ester.
Background technique
Tardive dyskinesia is a kind of central nervous system disease, and it is not autonomous to show as the appearance such as trunk, four limbs, face
Repetition abnormal motion.It is usually drug-induced by schizophrenia.In the treatment of schizophrenia, two-phase personality disorder and depression
In, antipsychotic drug can inhibit the dopamine receptor of big intracerebral, and this will lead to some intracorporal dopamine signal paths and goes out
Existing disorder.If these disorders occur to will result in the symptom of tardive dyskinesia in the region of brain control movement.
Valbenazine (NBI-98854, MT-5199) is researched and developed by U.S. Neurocrine Biosciences Inc,
It is Vesicular monamine transporter-2 (vesicular monoamine transporter 2, VMAT-2) inhibitor, can be reduced more
The secretory volume of bar amine, avoids dopamine signal path disorder, for treating the tardive dyskinesia (Tardive of adult patients
Dyskinesia, TD).As disclosed by WO2017/075340 patent application, Valbenazine is shown in chemical structure such as formula (I)
Compound, chemical name be (S) -2 amino -3- metliyl-butyric acid (2R, 3R, 11bR) -3- isobutyl group -9,10- dimethoxy -
1,3,4,6,7,11b- hexahydro -2H- pyrido [2,1-a] isoquinolin-2-yl ester (English name are as follows: (S) -2-amino-3-
methyl-butyric acid(2R,3R,116R)-3-isobutyl-9,10-dimethoxy-l,3,4,6,7,1lb-
hexahydro-2H-pyrido[2,l-a]isoquinolin-2-yl ester)。
Valbenazine obtained at present FDA it is granted and list drug trade name Ingrezza, the work of prescription
Property ingredient be Valbenazine toluene fulfonate (Valbenazine tosylate), as shown in Formula II, dosage form is oral capsule
Capsule, non-active ingredient include mannitol, partially pregelatinized starch, fumed silica and magnesium stearate, Valbenazine specification
For 40mg, the weight for being converted to its salt is then 73mg.
The oral preparation of pharmaceutically acceptable salt about Valbenazine, CN101553487 only generally disclose it
It can be made into powder, granule, pill, tablets and capsules etc., there has been no the reports of related new formulation at present.In view of tardy
The physical condition of property dyskinesia patient, it is abnormal difficult that common capsule, tablets and other formulations take patient, therefore, ability
A kind of domain urgently pharmaceutically acceptable salt new oral for being conducive to the Valbenazine that tardive dyskinesia patient uses
Preparation.
Oral disnitegration tablet is that one kind does not need water or only needs a small amount of water, without chewing, and tablet is placed in lingual surface, and it is fast to meet saliva
Speed disintegration, by means of power is swallowed, drug can enter the tablet of stomach action.After oral disnitegration tablet disintegration is swallowed, because saliva amount is few, drug
Particle is thin, can be uniformly distributed in stomach, adsorbs or be embedded in gastric mucosa, and uptake increases, will not be big because of gastric mucosa part dose
Stimulation is generated, there is comparable advantage to the patient for gulping down water difficulty, be the solid system that Abroad in Recent Years develops rapidly
Agent.
Tardive dyskinesia patient oral drugs are difficult, in order to improve the pharmaceutically acceptable salt of Valbenazine
For treating the compliance of tardive dyskinesia, the present invention provides the pharmaceutically acceptable salts of Valbenazine a kind of
Oral disintegrating tablet, disintegration rate is fast, and bioavilability height is rapid-action, and simple production process.
Summary of the invention
The present invention provides it is a kind of include the pharmaceutically acceptable salt such as compound of formula I oral disintegrating tablet,
The oral disintegrating tablet includes a effective amount of structure compound shown in formula I and pharmaceutically acceptable carrier, described
Pharmaceutically acceptable carrier includes dispersing agent.
In one embodiment of oral disintegrating tablet of the invention, the pharmaceutically acceptable carrier further includes diluent, collapses
Solve agent, corrigent and lubricant.
In one embodiment of oral disintegrating tablet of the invention, the pharmaceutically acceptable salt is the toluene of compound of formula I
Sulfonate；Preferably, the toluene fulfonate is as shown in Formula II.
In one embodiment of oral disintegrating tablet of the invention, each component of the oral disintegrating tablet is described by weight percentage
It is compound of formula I 30~40%, the diluent 8~20%, the dispersing agent 30~45%, the disintegrating agent 3~15%, described
Lubricant 0.5~1.5%, corrigent 2~5%；Preferably, each component weight fraction ratio of the oral disintegrating tablet are as follows: the Formulas I
Close object 32~37%, the diluent 9~15%, the dispersing agent 32~40%, the disintegrating agent 4~15%, the flavoring
Agent 2~4%, the lubricant 0.8~1.0%.
The diluent of this field routine can be selected in oral disintegrating tablet of the invention.The diluent may include microcrystalline cellulose, portion
Divide one or more mixtures of pregelatinized starch, mannitol, lactose.
The dispersing agent of this field routine can be selected in oral disintegrating tablet of the invention.Dispersing agent of the present invention can be described as resistive connection again
Block agent.The dispersing agent includes one or more mixtures of calcium phosphate, calcium silicates, calcium carbonate, aluminium-magnesium silicate.It is preferred that
Ground, the dispersing agent include calcium phosphate, calcium silicates.High porosity is made here by dispersing agent is added in prescription in the present invention
Internal structure, reduce disintegrating agent dosage, also can be reduced sand type while guaranteeing hardness.
The disintegrating agent of this field routine can be selected in oral disintegrating tablet of the invention.The disintegrating agent includes starch, modified starch, fibre
Tie up plain powder, crospovidone, Sodium Hydroxymethyl Stalcs, croscarmellose sodium, low-substituted hydroxypropyl cellulose, alginic acid,
One or more mixtures of hydroxypropyl methylcellulose；Preferably, the disintegrating agent include low-substituted hydroxypropyl cellulose,
One or both of crospovidone mixture.
Corrigent, lubricant and the colorant of this field routine can be selected in oral disintegrating tablet of the invention.The corrigent packet
Include one or more mixtures of Sucralose, citric acid, Aspartame, stevioside glycosides, saccharin sodium；The lubricant
Including one or both of magnesium stearate, talcum powder mixture；The colorant include amaranth, lemon yellow, famille rose and
It is one or more mixtures of indigo；Preferably, the colorant accounts for the 1-3% of the oral disintegrating tablet gross weight.
In one embodiment of oral disintegrating tablet of the invention, the mouth of the above-mentioned pharmaceutically acceptable salt such as compound of formula I
Disintegrating tablet comprising following component:
In one embodiment of oral disintegrating tablet of the invention, the dispersing agent is calcium silicates or calcium phosphate.
In one embodiment of oral disintegrating tablet of the invention, the disintegrating agent is that low-substituted hydroxypropyl cellulose or crosslinking are poly-
Tie up ketone；The diluent is mannitol or lactose.
In one embodiment of oral disintegrating tablet of the invention, the corrigent is Sucralose or Aspartame or citron
Acid.
The present invention provides a kind of method of oral disintegrating tablet described with direct compression method preparation,
Described method includes following steps:
1. the toluene fulfonate of compound of formula I and corrigent are pre-mixed；
2. by step, 1. mixture obtained is uniformly mixed with diluent, disintegrating agent, dispersing agent, colorant；
3. by step 2. mixture obtained and mix lubricant；
4. by step, 3. mixture tablet press machine obtained is tabletted, and the oral disintegrating tablet is made.
The present invention also provides a kind of methods of oral disintegrating tablet described with the preparation of dry granulation method, and it includes following steps:
The method includes method one or methods two:
The method one includes the following steps:
1. the toluene fulfonate of compound of formula I and diluent, dispersing agent, partial disintegration agent, partial lubrication agent, part flavoring
Agent premixing；
2. by step, 1. mixture obtained is added in dry granulating machine, is prepared particle, whole grain, is collected particle；
3. by step, 2. particle obtained is uniformly mixed with remaining disintegrating agent, residue corrigent；
4. by step, 3. mixture obtained is mixed with rest lubricant；
5. the oral disintegrating tablet is made by tabletted in step 4. mixture addition tablet press machine obtained；
The method two includes the following steps:
1. the toluene fulfonate of compound of formula I and diluent, dispersing agent, partial disintegration agent, partial lubrication agent, part flavoring
Agent premixing；
2. by step, 1. mixture obtained is added in dry granulating machine, is prepared particle, whole grain, is collected particle；
3. 2. particle obtained is uniformly mixed step with the diluent, remaining disintegrating agent, remaining corrigent separately added；
4. by step, 3. mixture obtained is mixed with rest lubricant；
5. the oral disintegrating tablet is made by tabletted in step 4. mixture addition tablet press machine obtained.
In one embodiment of oral disintegrating tablet of the invention, in the method one or method two, the step 2. in
Particle is crossed into 50 meshes in the whole grain step.
In one embodiment of oral disintegrating tablet of the invention, the step 2. in 300 μm of collected grain diameter <.
In one embodiment of oral disintegrating tablet of the invention, 4. middle incorporation time is 3-5min to the step.
This field conventional raw material and method preparation also can be used in oral disintegrating tablet of the invention.
On the basis of common knowledge of the art, above-mentioned each optimum condition, can any combination to get each preferable reality of the present invention
Example.
The reagents and materials used in the present invention are commercially available.
The positive effect of the present invention is that: the pharmaceutically acceptable salt of Valbenazine provided by the invention
Oral disintegrating tablet improves the compliance for the treatment of tardive dyskinesia.High hole is made by the way that dispersing agent is added in prescription in the present invention
The internal structure of gap rate, reduce disintegrating agent dosage, reduce sand type, guarantee the higher tablet of hardness also can fater disintegration, compare
Single disintegrating agent has disintegration effect well.Oral disintegrating tablet disintegration rate of the invention is fast, and bioavilability height is rapid-action, complies with
Property is good, and simple production process avoids the damp and hot influence to medicine stability using direct tablet compressing or dry granulation.
Detailed description of the invention
Fig. 1 is the dissolution curve comparison diagram of the embodiment of the present invention and commercially available capsule.
Specific embodiment
The present invention is further illustrated below by the mode of embodiment, but does not therefore limit the present invention to the reality
It applies among a range.In the following examples, the experimental methods for specific conditions are not specified, according to conventional methods and conditions, or according to quotient
The selection of product specification.
Valbenazine tosylate in following embodiment is limited from Suzhou roc rising sun medical sci-tech as shown in Formula II
Commercially available gained at company, can also be according to this field published method preparation.
1 direct compression method of embodiment
Prescription:
Preparation process is as follows:
1. Valbenazine tosylate (Formula II compound) is mixed in advance with Sucralose, citric acid equal increments
It is even；
2. by step, 1. mixture obtained is mixed with mannitol, calcium silicates, low-substituted hydroxypropyl cellulose, amaranth
It is even；
3. by step 2. mixture obtained with magnesium stearate mixing 3-5 minutes；
4. by step, 3. mixture tablet press machine obtained is tabletted, and oral disintegrating tablet piece is made and weighs about 202mg, hardness about 2-
4kg。
2 direct compression method of embodiment
Prescription:
Preparation process is as follows:
1. by Valbenazine tosylate (Formula II compound) and Aspartame, blackcurrant powdered flavor equal increments
Premix is uniform；
2. by step, 1. mixture obtained is uniformly mixed with lactose, calcium silicates, crospovidone, amaranth；
3. by step 2. mixture obtained with magnesium stearate mixing 3-5 minutes；
4. by step, 3. mixture tablet press machine obtained is tabletted, and oral disintegrating tablet piece is made and weighs about 202mg, hardness about 2-
4kg。
3 dry granulation method of embodiment
Prescription:
Preparation process is as follows:
1. by Valbenazine tosylate (Formula II compound) and interior plus part mannitol, calcium phosphate, low substitution
Hydroxypropyl cellulose, Sucralose, magnesium stearate premix are uniform；
2. by step, 1. mixture obtained is added in dry granulating machine, and suitable pressure roller spacing, charging rate, sky is arranged
Air pressure with crushing speed, crosses 50 mesh sieves, collects 300 μm of < of particle by force；
3. by step, 2. particle obtained is uniformly mixed with the crospovidone of Extra Section, Sucralose；
4. by step, 3. mixture obtained mixes 5 minutes with magnesium stearate；
5. oral disintegrating tablet piece is made and weighs about 207mg, hardness by tabletted in step 4. mixture addition tablet press machine obtained
About 2-4kg.
4 dry granulation method of embodiment
Prescription:
Preparation process is as follows:
1. by Valbenazine tosylate (Formula II compound) and interior plus part microcrystalline cellulose, calcium silicates, three
Chlorine sucrose, magnesium stearate premix are uniform；
2. by step, 1. mixture obtained is added in dry granulating machine, and suitable pressure roller spacing, charging rate, sky is arranged
Air pressure with crushing speed, crosses 50 mesh sieves, collects 300 μm of < of particle by force；
3. 2. particle obtained is uniformly mixed step with the mannitol of Extra Section, crospovidone, strawberry powdered flavor；
4. by step, 3. mixture obtained mixes 5 minutes with magnesium stearate；
5. oral disintegrating tablet piece is made and weighs about 223mg, hardness by tabletted in step 4. mixture addition tablet press machine obtained
About 2.5-5kg.
5 direct compression method of embodiment
Prescription:
Preparation process is as follows:
1. Valbenazine tosylate and Aspartame, vanilla powdered flavor equal increments are premixed uniform；
2. by step, 1. mixture obtained is uniformly mixed with mannitol, aluminium-magnesium silicate, crospovidone, amaranth；
3. by step 2. mixture obtained with magnesium stearate mixing 3-5 minutes；
4. by step, 3. mixture tablet press machine obtained is tabletted, and oral disintegrating tablet piece is made and weighs about 204mg, hardness about 2-
4kg。
Comparative example 1
Prescription:
Preparation process is as follows:
1. Valbenazine tosylate (Formula II compound) and Aspartame equal increments are premixed uniform；
2. by step, 1. mixture obtained is uniformly mixed with mannitol, crospovidone, amaranth；
3. by step, 2. mixture obtained mixes 3 minutes with magnesium stearate；
4. by step, 3. mixture tablet press machine obtained is tabletted, and oral disintegrating tablet piece is made and weighs about 215mg, hardness about 2-
4kg。
Comparative example 2
Prescription:
Preparation process is as follows:
1. Valbenazine tosylate (Formula II compound) and Aspartame equal increments are premixed uniform；
2. by step, 1. mixture obtained is mixed with mannitol, low-substituted hydroxypropyl cellulose, crospovidone, amaranth
It closes uniform；
3. by step, 2. mixture obtained mixes 3 minutes with magnesium stearate；
4. by step, 3. mixture tablet press machine obtained is tabletted, and oral disintegrating tablet piece is made and weighs about 215mg, hardness about 2-
4kg。
Effect example
(1) friability, disintegration time and mouthfeel experiment
For the performance for evaluating oral disintegrating tablet, this experiment is checked referring to four 0921 disintegration time limiteds of general rule of version Chinese Pharmacopoeia in 2015
Method investigates the disintegration time of embodiment and comparative example；Referring to four 0923 tablet friability of the general rule inspections of version Chinese Pharmacopoeia in 2015
Cha Fa investigates the friability of embodiment and comparative example；Multidigit volunteer has attempted the mouthfeel of oral disintegrating tablet.Testing result such as 1 institute of table
Show:
Table 1
It can be seen that the embodiment of the present invention after being added to dispersing agent from above-mentioned experimental result, it is general relative to only including
The comparative example of logical disintegrating agent, under the premise of guaranteeing hardness and friability, disintegration effect, mouthfeel are more preferable, significantly improve
Compliance.
(2) Dissolution experiments
This product dissolving-out method referring to disclosed in FDA, this experiment have carried out dissolution curve to self-control oral disintegrating tablet and commercially available capsule
Comparison, leaching condition are as shown in table 2:
Table 2
| Method | Paddle method (capsule should add sedimentation basket) |
| Revolving speed | 50rpm |
| Dissolution medium | 0.1M hydrochloric acid solution |
| Set temperature | 37℃ |
| Medium volume | 900ml |
| Sample time | 5、10、15、30、45min |
The Valbenazine tosylate in embodiment and comparative example is contained using following high performance liquid chromatography
Measure percentage test.The high performance liquid chromatography uses C18 column, fades in 2.5 minutes from 10% acetonitrile solution
90% acetonitrile solution is eluted, and is kept for 90% acetonitrile 1 minute, wherein acetonitrile and water all contain 0.025%TFA, wherein examining
Survey wavelength is 254nm, and flow velocity is 1.0mL/ points, and column temperature is 20 DEG C.
Accumulative dissolution dissolution rate detect as shown in table 3 according to above-mentioned dissolving-out method and HPLC testing conditions:
Table 3
Dissolution curve is as shown in Figure 1.Fig. 1 abscissa is time (min), and ordinate is accumulative dissolution (%).By dissolving out
Analysis of experimental results, the dissolution rate > 85% of this experiment oral disintegrating tablet 15min obtained, belongs to the preparation extremely fast discharged, dissolves out
Rate is apparently higher than original and grinds capsule.
The foregoing is merely illustrative of the preferred embodiments of the present invention, the substantial technological content model being not intended to limit the invention
It encloses, substantial technological content of the invention is broadly defined in the scope of the claims of application, any technology that other people complete
Entity or method also or a kind of equivalent change, will if identical with defined in the scope of the claims of application
It is considered as being covered by among the scope of the claims.
Claims (10)
1. a kind of includes the oral disintegrating tablet of the pharmaceutically acceptable salt such as compound of formula I,
The oral disintegrating tablet includes a effective amount of structure compound shown in formula I and pharmaceutically acceptable carrier, the pharmacy
Upper acceptable carrier includes dispersing agent.
2. the oral disintegrating tablet of such as pharmaceutically acceptable salt of compound of formula I according to claim 1, wherein described pharmaceutically
The carrier of receiving further includes diluent, disintegrating agent, corrigent and lubricant.
3. the oral disintegrating tablet of such as pharmaceutically acceptable salt of compound of formula I according to claim 1, wherein described pharmaceutically
The salt of receiving is the toluene fulfonate of compound of formula I.
4. the oral disintegrating tablet of such as pharmaceutically acceptable salt of compound of formula I according to claim 2, wherein the oral disintegrating tablet
Each component be by weight percentage the compound of formula I 30~40%, the diluent 8~20%, the dispersing agent 30~
45%, the disintegrating agent 3~15%, the lubricant 0.5~1.5%, corrigent 2~5%；Preferably, the oral disintegrating tablet
Each component weight fraction ratio are as follows: the compound of formula I 32~37%, the diluent 9~15%, the dispersing agent 32~
40%, the disintegrating agent 4~15%, the corrigent 2~4%, the lubricant 0.8~1.0%.
5. the oral disintegrating tablet of such as pharmaceutically acceptable salt of compound of formula I according to claim 2, wherein the diluent packet
Include one or more mixtures of microcrystalline cellulose, partially pregelatinized starch, mannitol, lactose.
6. the oral disintegrating tablet of such as pharmaceutically acceptable salt of compound of formula I according to claim 1, wherein the dispersing agent packet
Include one or more mixtures of calcium phosphate, calcium silicates, calcium carbonate, aluminium-magnesium silicate, it is preferable that the dispersing agent includes
Calcium phosphate or calcium silicates.
7. the oral disintegrating tablet of such as pharmaceutically acceptable salt of compound of formula I according to claim 2, wherein the disintegrating agent packet
Include starch, modified starch, cellulose powder, crospovidone, Sodium Hydroxymethyl Stalcs, croscarmellose sodium, low substitution hydroxyl
One or more mixtures of propyl cellulose, alginic acid, hydroxypropyl methylcellulose；Preferably, the disintegrating agent includes
One or both of low-substituted hydroxypropyl cellulose, crospovidone mixture；
And/or the corrigent includes one of Sucralose, citric acid, Aspartame, stevioside glycosides, saccharin sodium or two
Kind or more mixture；
And/or the lubricant includes one or both of magnesium stearate, talcum powder mixture；
Preferably, the pharmaceutically acceptable carrier of the oral disintegrating tablet further includes colorant, and the colorant includes amaranth, lemon
Lemon is yellow, carmine and one or more mixtures of indigo；It is highly preferred that the colorant accounts for the oral disintegrating tablet gross weight
1-3%.
8. any one of according to claim 1 as compound of formula I pharmaceutically acceptable salt oral disintegrating tablet comprising it is as follows
Component:
Preferably, the dispersing agent is calcium silicates or calcium phosphate；The disintegrating agent is that low-substituted hydroxypropyl cellulose or crosslinking are poly-
Tie up ketone；The diluent is mannitol or lactose；The corrigent is Sucralose or Aspartame or citric acid.
9. a kind of method for preparing oral disintegrating tablet according to claims 1-8,
Described method includes following steps:
1. the toluene fulfonate of compound of formula I and corrigent are pre-mixed；
2. by step, 1. mixture obtained is uniformly mixed with diluent, disintegrating agent, dispersing agent, colorant；
3. by step 2. mixture obtained and mix lubricant；
4. by step, 3. mixture tablet press machine obtained is tabletted, and the oral disintegrating tablet is made.
10. a kind of method for preparing oral disintegrating tablet according to claims 1-8,
The method includes method one or methods two:
The method one includes the following steps:
1. the toluene fulfonate of compound of formula I and diluent, dispersing agent, partial disintegration agent, partial lubrication agent, part corrigent are pre-
Mixing；
2. by step, 1. mixture obtained is added in dry granulating machine, is prepared particle, whole grain, is collected particle；
3. by step, 2. particle obtained is uniformly mixed with remaining disintegrating agent, residue corrigent；
4. by step, 3. mixture obtained is mixed with rest lubricant；
5. the oral disintegrating tablet is made by tabletted in step 4. mixture addition tablet press machine obtained；
The method two includes the following steps:
2. the toluene fulfonate of compound of formula I and diluent, dispersing agent, partial disintegration agent, partial lubrication agent, part corrigent are pre-
Mixing；
2. by step, 1. mixture obtained is added in dry granulating machine, is prepared particle, whole grain, is collected particle；
3. 2. particle obtained is uniformly mixed step with the diluent, remaining disintegrating agent, remaining corrigent separately added；
4. by step, 3. mixture obtained is mixed with rest lubricant；
5. the oral disintegrating tablet is made by tabletted in step 4. mixture addition tablet press machine obtained.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710858860.2A CN109528665A (en) | 2017-09-21 | 2017-09-21 | A kind of oral disintegrating tablet of drug and preparation method thereof for treating tardive dyskinesia |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11339158B2 (en) | 2017-12-26 | 2022-05-24 | Crystal Pharmaceutical (Suzhou) Co., Ltd. | Crystalline form of valbenazine ditosylate, processes for preparation thereof and use thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1827089A (en) * | 2005-02-28 | 2006-09-06 | 上海艾力斯医药科技有限公司 | Fine granules containing acid-labile medicine and preparation thereof |
| WO2016210180A2 (en) * | 2015-06-23 | 2016-12-29 | Neurocrine Biosciences, Inc. | Vmat2 inhibitors for treating neurological diseases or disorders |
| CN107072997A (en) * | 2014-11-11 | 2017-08-18 | 盐野义制药株式会社 | Multilayer tablet containing the medicine to photo-labile |
-
2017
- 2017-09-21 CN CN201710858860.2A patent/CN109528665A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1827089A (en) * | 2005-02-28 | 2006-09-06 | 上海艾力斯医药科技有限公司 | Fine granules containing acid-labile medicine and preparation thereof |
| CN107072997A (en) * | 2014-11-11 | 2017-08-18 | 盐野义制药株式会社 | Multilayer tablet containing the medicine to photo-labile |
| WO2016210180A2 (en) * | 2015-06-23 | 2016-12-29 | Neurocrine Biosciences, Inc. | Vmat2 inhibitors for treating neurological diseases or disorders |
Non-Patent Citations (1)
| Title |
|---|
| 孟胜男 等: "《药剂学》", 31 March 1978, 中国医药科技出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11339158B2 (en) | 2017-12-26 | 2022-05-24 | Crystal Pharmaceutical (Suzhou) Co., Ltd. | Crystalline form of valbenazine ditosylate, processes for preparation thereof and use thereof |
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