CN108078933A - A kind of tolvaptan dispersible tablet and preparation method thereof - Google Patents
A kind of tolvaptan dispersible tablet and preparation method thereof Download PDFInfo
- Publication number
- CN108078933A CN108078933A CN201711275779.8A CN201711275779A CN108078933A CN 108078933 A CN108078933 A CN 108078933A CN 201711275779 A CN201711275779 A CN 201711275779A CN 108078933 A CN108078933 A CN 108078933A
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- CN
- China
- Prior art keywords
- tolvaptan
- dispersible tablet
- tablet according
- dosage
- disintegrant
- 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.)
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Classifications
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
Abstract
The invention discloses a kind of tolvaptan Diskets.Using tolvaptan as raw material, auxiliary material is added in, is prepared into tolvaptan dispersible tablet.Disintegration is fast, it is fast to absorb, bioavilability height；It is convenient to take；Enteron aisle residual is few, few side effects；It is sweet and aromatic, it is particularly easy to improve patient's drug compliance.
Description
Technical field
The present invention relates to a kind of tolvaptan novel form, more particularly to be tolvaptan dispersible tablet and preparation method thereof.
Background technology
Tolvaptan is to develop non-peptides selectivity antidiuretic hormone V2 receptor antagonists by Otsuka companies, 2009 5
Moon FDA approval tolvaptan piece（Tolvaptan, Samsca）Hyponatremia is treated, is uniquely to be approved to treat the oral type of the disease
Selective vasopressin antagonists.It is mainly used for treating comprehensive by congestive heart failure, hepatic sclerosis and antidiuretic hormone secretion deficiency
Hyponatremia caused by simulator sickness.The multinomial randomized clinical control study that CHF treatments are used for for this product reported in recent years carries
Show, oral tolvaptan can raise Na ion concentration in blood plasma, and extra moisture is helped to be discharged from urine, can substantially reduced trouble
Person's weight and oedema, and blood electrolyte balance is not destroyed.Tolvaptan better tolerance is not necessarily limited the intake of water in treatment.With
Being approved for tolvaptan piece, a kind of doctor's new selections again more to treatment hyponatremia.【Products characteristics】Tolvaptan is
Uniquely it is approved to treat the oral type selectivity vasopressin antagonists of the disease, diuresis is strong, and without the increasing of electrolyte excretion
Add, available for treating various edema diseases, hyponatremia and patients with heart failure.The study found that when Na ion concentration drop in blood plasma
When low, in order to which the Na ion concentration of intraor extracellular is kept to balance, extracellular liquid will enter into the cell, this like cell will
Swelling.When brain cell swelling, the symptom that may result in various hyponatremia occurs.Including dizzy, weak, headache, nausea, consciousness
Entanglement and consciousness decrement and generation of fainting from fear.Serious hyponatremia can cause stupor and death, and tolvaptan piece is in weight at present
It spends in low blood sodium patient also without corresponding research.Tolvaptan piece can raise Na ion concentration in blood plasma, help extra water
Divide and discharged from urine.In clinical studies, this product is compared with placebo, hence it is evident that increases the Na ion concentration in patients blood plasma.
The black surround warning of tolvaptan piece must take for patient in the hospital of the close monitoring of concentration of serum sodium.Because concentration of serum sodium is such as
Fruit is raised too fast will to cause serious Osmotic Demyelination Syndrome to occur.Tolvaptan is non-peptide by the exploitation of Otsuka companies
Class AVP2 receptor antagonists, it is only necessary to 1 times a day take orally.Report in recent years it is multinomial for this product for CHF treatments it is clinical with
Machine comparative study is prompted, the substantially reduced patient's weight of oral tolvaptan energy and oedema, and does not destroy blood electrolyte balance, and
The concurrent low blood sodium of CHF patient can effectively be raised.Tolvaptan better tolerance is not necessarily limited the intake of water in treatment.It is common not
Good reaction is dry, thirsty sense, dizzy, nauseous, low blood pressure etc..The medicine lists in the U.S., and price is every（15mg）500 is beautiful
Gold.
Dispersible tablet is a kind of quick-effective preparation, due to its distinctive advantage, has been had been to be concerned by more and more people.It can add in
Solubilizer；The dissolution rate of tolvaptan insoluble drug can be improved, is suitable for taking.Piece is made for the difficult drug of disintegration
It can be conducive to absorb.The characteristics of piece：1. disintegration is fast, it is fast to absorb, bioavilability height；2. 3. enteron aisle residual convenient to take is few, secondary
Effect is few.
The content of the invention
The object of the present invention is to provide a kind of tolvaptan dispersible tablets and preparation method thereof.
Objects of the present invention are achieved through the following technical solutions.
Tolvaptan dispersible tablet of the present invention is by as follows into being grouped into（Weight percent）：
| Tolvaptan | 1-20% |
| Filler | 80-90% |
| Disintegrant | 8-28% |
| Adhesive | 0.1-6% |
| Solubilizer | 0.1-6% |
| Lubricant | 0.5-5%。 |
It is above the basic prescription of the present invention, suitably can be adjusted and deleted according to actual needs.
Tolvaptan is active ingredient, preferred content scope 1-10%, further preferred scope 1-5%.It is held in the palm in unit formulation
Cut down general smooth dosage 10-120mg, preferred dose 10-100mg, preferred dosage is 10,20,30,50mg.
Due to dispersible tablet requirement can be disintegrated rapidly in water it is homodisperse, have that convenient to take, disintegration is rapid, it is fast to absorb and
The features such as bioavilability is high.Therefore it is the key that prepare piece to the selection of supplementary product kind and its performance.Inventor is by multiple
Experiment, it is determined that be suitble to the pharmaceutic adjuvant and its dosage of tolvaptan dispersible tablet.
Filler selection is used for increasing the weight and volume of piece, shaping and divided dose in order to preparation.It is filled out in the present invention
Fill the mixture that agent is selected from one or more of lactose, sucrose, microcrystalline cellulose, pregelatinized starch, dextrin etc..Amount ranges
It is preferred that 80-90%, particularly preferred 80-85%.
Disintegrant is selected from the pharmaceutic adjuvants such as low-substituted hydroxypropyl cellulose, crospovidone.Dosage preferred 5-50%, it is especially excellent
Select 5-10%.
The selection of the species and dosage of solubilizer dissolves out most important for this preparation.The solubilizer of the present invention selects dodecane
One of base sodium sulphate, Macrogol 6000, Macrogol 4000, Tween 80, polysorbate40, sorbester p18, span 40 are wherein several
The mixture of kind further masks the bad strange taste of tolvaptan, improves the mouthfeel of piece.
Lubricant is selected from the mixture of one or more of superfine silica gel powder, magnesium stearate, talcum powder.
The present invention also provides the preparation methods of tolvaptan dispersible tablet.Tolvaptan dispersible tablet of the present invention can be straight with powder
Connect pressed disc method preparation.Direct powder compression preparation process is：By tolvaptan and filler（Such as lactose）, disintegrant, increasing
Solvent, adhesive and mix lubricant it is uniform after, direct powder compression.
Tolvaptan dispersible tablet disintegration of the present invention is fast, absorbs fast, bioavilability height；It is convenient to take；Enteron aisle residual is few, secondary
Effect is few；It is sweet, without tolvaptan off-odor and aromatic, it is particularly easy to improve patient's drug compliance.
Specific embodiment
Embodiment l
Prescription：
Preparation method：
（1）By tolvaptan powder（200 mesh）With cane sugar powder（150 mesh）Equal increments are uniformly mixed, and obtain mixture A；
（2）After remaining auxiliary material is crossed 200 mesh sieves, equal increments are uniformly mixed, and obtain mixture B；
（3）By mixture A and mixture B by equal increments method after mixing, direct tablet compressing.
Embodiment 2
Prescription：
Preparation method：
（1）By tolvaptan powder（200 mesh）With lactose powder（150 mesh）Equal increments are uniformly mixed, and obtain mixture A；
（2）After remaining auxiliary material is crossed 200 mesh sieves, equal increments are uniformly mixed, and obtain mixture B；
（3）By mixture A and mixture B by equal increments method after mixing, direct tablet compressing.
Embodiment 3
Prescription：
Preparation method：
（1）By tolvaptan powder（200 mesh）With lactose powder（150 mesh）Equal increments are uniformly mixed, and obtain mixture A；
（2）After remaining auxiliary material is crossed 200 mesh sieves, equal increments are uniformly mixed, and obtain mixture B；
（3）By mixture A and mixture B by equal increments method after mixing, direct tablet compressing.
Embodiment 4
Prescription：
Preparation method：
（1）By tolvaptan powder（200 mesh）With lactose powder（150 mesh）Equal increments are uniformly mixed, and obtain mixture A；
（2）After remaining auxiliary material is crossed 200 mesh sieves, equal increments are uniformly mixed, and obtain mixture B；
（3）By mixture A and mixture B by equal increments method after mixing, direct tablet compressing.
Invention formulation and technology prepares the study on the stability of sample：
Sample prepared by embodiment 1, embodiment 2, embodiment 3 and embodiment 4 is respectively placed in stability test case, is set
Temperature carries out accelerating within three months to investigate under the conditions of 40 DEG C, relative humidity 75%RH.
Using disintegration time limited as inspection target, it was demonstrated that the science for the tablet recipe technique invented.
Tolvaptan raw material used in above example is Pfizer's medicine company production；Auxiliary material supply producer is Ka Lekang pharmacy, moral
Gu match rule medicine, Le Jiawen pharmacy, International Specialty Products pharmaceutical Co. Ltd and Huainan mountains and rivers pharmaceutical Co. Ltd.
Claims (9)
1. a kind of tolvaptan dispersible tablet, is made of following weight percent composition：
2. tolvaptan dispersible tablet according to claim 1, wherein described：
Filler is selected from the mixture of one or more of microcrystalline cellulose, lactose, sucrose, pregelatinized starch, dextrin etc.；
Disintegrant is in low-substituted hydroxypropyl methylcellulose, crospovidone, sodium carboxymethyl starch, croscarmellose sodium
One of or wherein several mixtures；
Adhesive is selected from povidone, height substitutes one of hydroxypropylcellulose, gelatine size, starch slurry, sodium carboxymethylcellulose or it
In several mixtures；
Lubricant is selected from the mixture of one or more of superfine silica gel powder, magnesium stearate, talcum powder.
3. tolvaptan dispersible tablet according to claim 2, wherein the tolvaptan content range 1-20%.
4. tolvaptan dispersible tablet according to claim 2, wherein the filler loading scope 80-90%.
5. tolvaptan dispersible tablet according to claim 2, wherein the disintegrant dosage 5-20%.
6. tolvaptan dispersible tablet according to claim 2, wherein described adhesive dosage 0.5-2%.
7. the tolvaptan dispersible tablet according to any claim in claim 3-6, wherein：Tolvaptan content range
1-20%；Filler loading 80-90%；Disintegrant dosage 5-10%；Binder dosage 0.5-2%, solubilizer dosage 0.5-2%.
8. tolvaptan dispersible tablet according to claim 1, wherein the tolvaptan unit dose 10-120mg.
9. the preparation method of tolvaptan dispersible tablet described in claim 1, using direct powder compression, by tolvaptan with filling out
Fill agent, disintegrant, solubilizer, adhesive and mix lubricant it is uniform after, direct powder compression.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711275779.8A CN108078933A (en) | 2017-12-06 | 2017-12-06 | A kind of tolvaptan dispersible tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711275779.8A CN108078933A (en) | 2017-12-06 | 2017-12-06 | A kind of tolvaptan dispersible tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108078933A true CN108078933A (en) | 2018-05-29 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711275779.8A Pending CN108078933A (en) | 2017-12-06 | 2017-12-06 | A kind of tolvaptan dispersible tablet and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109528636A (en) * | 2018-12-20 | 2019-03-29 | 常州市阳光药业有限公司 | Tolvaptan oral administration solution and preparation method thereof |
| CN112121051A (en) * | 2020-09-30 | 2020-12-25 | 郑州大学 | Application of mozavatan in preparation of anti-digestive tract tumor medicine |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102114001A (en) * | 2009-12-30 | 2011-07-06 | 北京德众万全医药科技有限公司 | Orally administered solid preparation containing tolvaptan |
| CN106074406A (en) * | 2016-06-12 | 2016-11-09 | 佛山市腾瑞医药科技有限公司 | A kind of Vonoprazan fumarate dispersible tablet and preparation method thereof |
-
2017
- 2017-12-06 CN CN201711275779.8A patent/CN108078933A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102114001A (en) * | 2009-12-30 | 2011-07-06 | 北京德众万全医药科技有限公司 | Orally administered solid preparation containing tolvaptan |
| CN106074406A (en) * | 2016-06-12 | 2016-11-09 | 佛山市腾瑞医药科技有限公司 | A kind of Vonoprazan fumarate dispersible tablet and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109528636A (en) * | 2018-12-20 | 2019-03-29 | 常州市阳光药业有限公司 | Tolvaptan oral administration solution and preparation method thereof |
| CN112121051A (en) * | 2020-09-30 | 2020-12-25 | 郑州大学 | Application of mozavatan in preparation of anti-digestive tract tumor medicine |
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| PB01 | Publication | ||
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Application publication date: 20180529 |