CN107224430A - A kind of pharmaceutical composition of hydrochloric Ramosetron - Google Patents
A kind of pharmaceutical composition of hydrochloric Ramosetron Download PDFInfo
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- CN107224430A CN107224430A CN201610178048.0A CN201610178048A CN107224430A CN 107224430 A CN107224430 A CN 107224430A CN 201610178048 A CN201610178048 A CN 201610178048A CN 107224430 A CN107224430 A CN 107224430A
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
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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
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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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
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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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
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- Pharmacology & Pharmacy (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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Abstract
A kind of pharmaceutical composition of hydrochloric Ramosetron, the invention provides the pharmaceutical composition of a kind of Ramosetron of tablet form or its pharmaceutically-acceptable salts.It is made up of label with coating, the label is made up of Ramosetron or its pharmaceutically-acceptable salts, stabilizer, filler, disintegrant, adhesive, label lubricant, and the coating includes polyvinyl alcohol, polyethylene glycol, titanium dioxide.Described pharmaceutical composition has good stability under high humidity environment.
Description
Technical field
The present invention is field of pharmaceutical preparations, more particularly relates to a kind of tablet form pharmaceutical composition containing Ramosetron.
Background technology
Ramosetron HCl (Ramosetron Hydrochloride) is developed by Japanese Astellas drugmaker, commercial preparation master
There are 3 kinds of forms.The 1st kind of oral disintegrating tablet for 0.1mg dosage, for caused by treating cancer chemotherapy (such as using plus cisplatin in treatment)
The symptoms of digestive tract such as Nausea and vomiting.The 2nd kind of ordinary tablet for low dosage form (2.5 μ g or 5 μ g), the 3rd kind is low dosage
The oral disintegrating tablet of form (2.5 μ g or 5 μ g), all for treating diarrhea irritable bowel syndrome.
Due to the usage amount very little of active component in Ramosetron HCl preparation so that in preparation the stability control of active component into
For difficult point.
CN1723021A discloses a kind of Ramosetron or the preparation of its pharmaceutically acceptable salt, and said preparation is for oral
Stable solid composite medicament.More specifically disclose and citric acid, red di-iron trioxide, yellow are added into Ramosetron
Di-iron trioxide has static stabilization to it under temperature/humidity and light.
CN1764453A discloses a kind of pharmaceutical composition for treating Irritable bowel Syndrome, the pharmaceutical composition daily dose
Contain 0.001 to 0.05mg Ramosetron HCl or the Ramosetron of equimolar amounts or its pharmaceutically acceptable other salt conduct
Active component.
CN101516367A discloses a kind of Ramosetron preparation stablized under light illumination.By thunder unstable under light illumination not
The compound of the light of absorbable specific wavelength is mixed in department's fine jade or its pharmaceutically acceptable salt and stable preparation is provided；It is main to use
In Orally disintegrating tablet.
The content of the invention
The invention discloses the pharmaceutical composition of a kind of Ramosetron of tablet form or its pharmaceutically-acceptable salts.
In a first aspect, the invention provides a kind of pharmaceutical composition containing Ramosetron or its pharmaceutically-acceptable salts, described group
Compound is tablet form, and the tablet is made up of label with coating, the label by Ramosetron or its pharmaceutically-acceptable salts,
Stabilizer, filler, disintegrant, adhesive, label lubricant composition, the coating include polyvinyl alcohol, polyethylene glycol,
Titanium dioxide.
Ramosetron pharmaceutically-acceptable salts, refer to that Ramosetron reacts to be formed normal with inorganic acid, organic acid or acidic amino acid
Advise nontoxic or low toxicity salt.For example, inorganic acid is selected from hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid etc.；Organic acid is selected from acetic acid, amber
Acid, tartaric acid, citric acid, maleic acid, the salt of the preparation such as fumaric acid, methanesulfonic acid, oxalic acid；Acidic amino acid be selected from glutamic acid,
Aspartic acid etc..It is preferred that, Ramosetron pharmaceutically-acceptable salts are Ramosetron HCl in the present invention；More specifically refer to thunder
Mo Siqiong is 1 with hydrochloric acid mol ratio：1 Ramosetron hydrochloride.
In the label of heretofore described tablet form pharmaceutical composition, every contains Ramosetron or its pharmaceutically-acceptable salts
0.002~0.006mg.Preferably contain 0.002~0.006mg of Ramosetron HCl, more preferably contain Ramosetron HCl
0.0025~0.005mg.
In the Ramosetron for the tablet form that the present invention is provided or the pharmaceutical composition of its pharmaceutically-acceptable salts, Ramosetron or its
The content of pharmaceutically-acceptable salts is low.The stability of Ramosetron or its pharmaceutically-acceptable salts, by auxiliary material or the shadow of external environment
Ring obvious.Stabilizer can stablize Ramosetron or its pharmaceutically-acceptable salts.
Stabilizer is selected from citric acid, citric anhydride, tartaric acid, malic acid in the present invention；It is preferred that the stabilizer be citric acid.
The mass ratio of the preferred stabilizer and Ramosetron or its pharmaceutically-acceptable salts is (48~200)：1.
Filler, alternatively referred to as diluent, main function are for increasing the weight and/or volume of pharmaceutical composition；Simultaneously can be with
Reduce the dose deviations of active component, improve compressibility.
Filler is selected from starch, pregelatinized starch, dextrin, lactose, microcrystalline cellulose, mannitol in the present invention；Preferably
Microcrystalline cellulose.The mass ratio of the preferred filler and Ramosetron or its pharmaceutically-acceptable salts is
(17000~27000)：1.
Microcrystalline cellulose is through the obtained powder of hydrolysis from pure cotton fiber；It is odorless, tasteless for white or off-white powder, by many
Hole particulate composition.It is divided into some specifications according to particle diameter is different with water content, such as trade name have 101 for Avicel microcrystalline cellulose,
102nd, 103,105,112,113,200,301,302 equal-specification.
Microcrystalline cellulose preferably possesses following property in the present invention：90~200 μm of average grain diameter；60 mesh sieves are crossed, residual quantity is not
Higher than 15%；200 mesh sieves are crossed, residual quantity is not higher than 55%.In the preferred present invention microcrystalline cellulose be Avicel PH-302,
Avicel PH-200 (trade name and model), or possess the microcrystalline cellulose of same or like property.This hair still more preferably
Bright middle microcrystalline cellulose is Avicel PH-302, Avicel PH-200 (trade name and model)；Most preferred microcrystalline cellulose is
Avicel PH-302 (trade name and model).《Pharmaceutic adjuvant handbook (fourth edition)》, English fiction is entitled《Handbook of
Pharmaceutical Excipients(Fourth Edition)》, Chemical Industry Press, page 129~133 is i.e. to microcrystalline cellulose
There is special introduction.
Disintegrant is to make tablet rapid material for being fragmented into fine particle in gastro-intestinal Fluid.
Disintegrant is selected from carboxymethyl cellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, cross-linked carboxymethyl fibre in the present invention
The plain sodium of dimension, low-substituted hydroxypropyl cellulose, PVPP；Preferably low-substituted hydroxypropyl cellulose.The preferred disintegration
The mass ratio of agent and filler is (6.5~16)：100.
Adhesive (or binder) is meant to giving stickiness without stickiness or the not enough material of stickiness, so that material is gathered into
The auxiliary material of grain.
Adhesive is selected from hydroxypropyl methylcellulose, hydroxypropylcellulose, PVP in the present invention；Preferably hydroxypropylcellulose.It is more excellent
The described adhesive of choosing and the mass ratio of filler are (2~3.5)：100.
Lubricant can reach under different use environments helps stream, anti-glutinous or lubrication effect.
Heretofore described label lubricant is selected from magnesium stearate, calcium stearate, stearic acid, talcum powder；Preferably stearic acid
Magnesium.The mass ratio of preferred the label lubricant and filler is (0.4~0.75)：100.
When tabletting obtains label, those skilled in the art can voluntarily determine to select the mould of suitable size according to existing knowledge
And determine hardness.For example, when Ramosetron in label or its pharmaceutically-acceptable salts are 0.002~0.003mg, it is preferred to use
5~6mm of diameter mould；When Ramosetron in label or its pharmaceutically-acceptable salts are 0.004~0.006mg, it is preferred to use
6~7mm of diameter mould.
According to the difference of coating material, the tablet of coating can be broadly divided into sugar coated tablet, Film coated tablets, Enteric coated tablets.The present invention
In, it is described to be coated the suitable coating that have negative effect to the dissolution rate of final preparation for known to, preferably film coating.
By film coating label can be made to possess sealing to be coated, to reach protection patient, clinical staff and moistureproof purpose.For example may be used
With by by disintegration/dissolution of formulation, stability, without substantial effect high polymer material and other auxiliary materials, (other auxiliary materials are for example selected
Self-plasticization agent, lubricant and optional pigment) it is dissolved in water or organic solvent, and this mixture is sprayed on label.
The present invention is coated to label as bag stomach dissolution type film-coating.It is preferred that coating of the present invention include polyvinyl alcohol, it is poly-
Ethylene glycol, titanium dioxide.Also include being coated lubricant in coating of the present invention；Also include colouring agent in coating of the present invention.
The coating lubricant is selected from magnesium stearate, calcium stearate, stearic acid, talcum powder；Preferably talcum powder.
Coating in the present invention, polyvinyl alcohol is as film forming agent, and polyethylene glycol is used as opacifier as plasticizer, titanium dioxide.
It is preferred that coating in, film forming agent, plasticizer, opacifier, be coated lubricant mass ratio be (30~60)：(2~10)：(5~20)：
(5~20).
The colouring agent is medicinal or food coloring, including but not limited to yellow iron oxide, No. 10 aluminum lakes of yellow, sunset yellow aluminium
Color lake, indigo aluminum lake.It is preferred that, the mass percent of colouring agent is 2~10% in coating.It is preferred that, it is coated in the present invention
Quality be label quality 3%~5%.
The pleasantly surprised discovery of inventor in the present invention, can improve the humidity resistance of pharmaceutical composition in coating containing polyvinyl alcohol；
Greatly improve stability of the pharmaceutical composition under high humidity environment.
Dissolution test can use following scheme in the present invention：Paddle method, rotating speed 50r/min, 500mL dissolution medium；Dissolution is situated between
Matter is selected from water, pH6.8, pH4.5, pH1.0；Sampling time point be 5,10,15,20,30,45min.In the present invention not
The dissolution test specialized uses dissolution medium for water, sampling time point 15min.The ramosetron hydrochloride department prepared according to the present invention
Accumulation dissolution of the fine jade piece in pH1.0, pH4.5, pH6.8 and water during 10min up to more than 75%, 15min dissolution are accumulated
Release is more than 80%.
Foundation《Chinese Pharmacopoeia》The regulation of version two in 2010, the disintegration time limited of common quick release tablet is 15min.According to this hair
The Ramosetron or the pharmaceutical composition of its pharmaceutically-acceptable salts of bright obtained tablet form, its disintegration time are no more than 5 minutes,
Preferably it is no more than 3 minutes.
Second aspect, the pharmaceutical composition containing Ramosetron or its pharmaceutically-acceptable salts that the present invention is provided, can be used for abdomen
Rush down the treatment of type intestinal irritable syndrome.
The third aspect, the invention provides a kind of Key works Drug packing combination containing tablet form pharmaceutical composition of the present invention.
The packaged combination is made up of the tablet form pharmaceutical composition of medicine packing box, package insert, aluminium-plastic bubble plate packing；It is described
Package insert, the tablet form pharmaceutical composition of aluminium-plastic bubble plate packing are placed in packing box.Further plastic-aluminum can also be steeped
The tablet form pharmaceutical composition of cover packaging is sealed in aluminium foil bag, and aluminium foil bag is placed in into Key works Drug packing together with package insert
In box；Sealed aluminium foil bag can further reach the moistureproof, purpose of lucifuge.
The Ramosetron of tablet form of the present invention or the pharmaceutical composition of its pharmaceutically-acceptable salts, although active component is (main
Medicine composition) usage amount very little；But possess good stability.Especially under high humidity environment, with ordinary packing shape
Formula is deposited, and has remained in that good stability.In the accelerated stabilities of 6 months are investigated, deposited in ordinary packing form,
Also good stability has been embodied.
Embodiment
The present invention is further illustrated below by the mode of embodiment, but following embodiments are not limiting the scope of the invention.
Embodiment 1
Weigh active component and auxiliary material according to the consumption of 2000, wherein every containing the μ g of Ramosetron HCl 2.5 (0.0025mg,
0.0033%), anhydrous citric acid 0.125mg (0.17%), microcrystalline cellulose 66mg (87.59%), low-substituted hydroxypropyl cellulose
7.5mg (9.95%), hydroxypropylcellulose 1.35mg (1.79%), magnesium stearate 0.375mg (0.5%).
Load weighted hydroxypropylcellulose is dissolved in purified water, binder solution (3%, w/w) is prepared.By Ramosetron HCl
Binder solution is added to citric acid, and is stirred, binder solution containing API is prepared.By microcrystalline cellulose, low substitution
Hydroxypropylcellulose is put into fluid bed, and spraying granulation is carried out with containing API binder solutions, and 10min is dried after granulation.Will fluidisation
The obtained particle of bed is mixed with magnesium stearate, obtains hybrid particles.By hybrid particles tabletting (diameter 5.5mm circle scrobicula moulds,
Hardness is controlled in 40-50N).
When the specifications and models of microcrystalline cellulose are different, particle made from fluid bed and by label made from hybrid particles tabletting
Property such as table 1.MCC, 102 two kinds of model fluidized bed granulations are difficult, and the fluffy adhesion of particle after granulation does not have
Mobility, particle can not tabletting.Granule fines are more after the fluidized bed granulation of microcrystalline cellulose 301, and mobility is bad, during tabletting
Piece weight less stable.There is preferable mobility, but crystallite after microcrystalline cellulose 200 and 302 two specification fluidized bed granulations
The tabletting time slice weight stability of cellulose 302 is better than microcrystalline cellulose 200.
Table 1
Embodiment 2
Microcrystalline cellulose 302 is fixed as according to composition similar to Example 1, preparation method, but by microcrystalline cellulose,
With in every respectively containing anhydrous citric acid 0.06mg, 0.12mg, 0.25mg, 0.5mg (be respectively API 24,48,100,
200 times of weight), prepare Ramosetron HCl label.Label is coated, it is hydroxypropyl methylcellulose, poly- second two to be coated composition
Alcohol, titanium dioxide, talcum powder, yellow iron oxide (composition be the same as Example 6).
Compare 4 kinds of prescriptions obtained Ramosetron HCl piece respectively, under acceleration conditions (40 DEG C ± 2 DEG C, 75%RH ± 5%RH,
30 days) about material, the change of content.As a result it is：Setting-out is accelerated to have for 30 days when containing 0.06mg anhydrous citric acids in every
Close material and increase obvious, remaining 3 prescription accelerates 30 days relevant materials of setting-out to increase unobvious.
Embodiment 3
Microcrystalline cellulose 302 is fixed as according to composition similar to Example 1, preparation method, but by microcrystalline cellulose,
(to account for the percentage score of microcrystalline cellulose weight containing low-substituted hydroxypropyl cellulose 4.5mg, 7.5mg, 10.5mg respectively in every
Not Wei 6.8%, 11.4,15.9%), prepare Ramosetron HCl label, during tabletting hardness control in 50-70N.
The label that the low-substituted hydroxypropyl cellulose of different amounts is made, has investigated its disintegration time, disintegration time be respectively 4min,
2min、2min.The label that three different amounts disintegrants are obtained, its disintegration time all meets medicinal requirement, but low substitution hydroxyl
Third cellulose is rapider for 7.5mg, 10.5mg label disintegration.The label that low-substituted hydroxypropyl cellulose is 10.5mg is found simultaneously
Fine powder is more after fluidized bed granulation, shows that disintegrant low-substituted hydroxypropyl cellulose does not have with microcrystalline cellulose during fluidized-bed spray granulation
It is completely combined.
Embodiment 4
Microcrystalline cellulose 302 is fixed as according to composition similar to Example 1, preparation method, but by microcrystalline cellulose,
(to account for the percentage of microcrystalline cellulose weight containing adhesive hydroxypropylcellulose 1.35mg, 1.8mg, 2.25mg respectively in every
Respectively 2%, 2.7%, 3.4%；Purify water consumption consistent with embodiment 1, average 43.5mg when being every granulation), prepare salt
Sour Ramosetron label.
It was found that after fluidized bed granulation, fluidized bed granulation particle is than more uniform when the equal content of adhesive sheet is 1.35mg, in tabletting,
Piece thickness is between 2.6-2.7mm, and hardness is 40-50N；Fluidized bed granulation particle is uniform when the equal content of adhesive sheet is 1.8mg,
Piece is thick proper with pressure；The equal content of adhesive sheet is that constantly fluidized bed granulation particle is larger by 2.25mg, has residual adhesion, presses
Piece time slice thickness 2.7-2.9mm, hardness is in 60-80N, and the disintegration time of tablet is 4.5min.3 different binder dosages are all
Meet the requirements, but adhesive sheet equal content is when every property is better than being 1.35mg, 2.25mg when being 1.8mg.
Embodiment 5
Weigh active component and auxiliary material according to the consumption of 2000, wherein every containing the μ g of Ramosetron HCl 5 (0.005mg,
0.005%), anhydrous citric acid 0.5mg (0.5%), the 86.6mg of microcrystalline cellulose 302 (86.6%), low-substituted hydroxypropyl cellulose
10mg (10%), hydroxypropylcellulose 2.4mg (2.4%), magnesium stearate 0.5mg (0.5%).
Load weighted hydroxypropylcellulose is dissolved in purified water, binder solution (4%, w/w) is prepared.By Ramosetron HCl
Binder solution is added to citric acid, and is stirred, binder solution containing API is prepared.By microcrystalline cellulose, low substitution
Hydroxypropylcellulose is put into fluid bed, and spraying granulation is carried out with containing API binder solutions, and 10min is dried after granulation.Will fluidisation
The obtained particle of bed is mixed with magnesium stearate, obtains hybrid particles.By hybrid particles tabletting (diameter 6.5mm circle scrobicula moulds,
Hardness is controlled in 50-70N).
As a result show that the mobility of particle that fluidized bed granulation is obtained is good, the label that tabletting is obtained is unilateral bright and clean, and disintegration time is
3min。
Embodiment 6
According to prescription and method in embodiment 5, label is prepared according to 3000 sheet gauge moulds；Obtain label and be divided into 3 parts, be coated respectively.
It is coated 6-1：Hydroxypropyl methylcellulose, polyethylene glycol, titanium dioxide, talcum powder, yellow iron oxide, mass percent difference
It is about 50%, about 10%, about 15%, about 15%, about 10%.
It is coated 6-2：Polyvinyl alcohol, polyethylene glycol, titanium dioxide, talcum powder, yellow iron oxide, mass percent is respectively
About 50%, about 10%, about 15%, about 15%, about 10%.
It is coated 6-3：Stomach dissolution type Opadry 85F620005 (the coating premixing flour of commercialization), it is its main component polyvinyl alcohol, poly-
Ethylene glycol, titanium dioxide, talcum powder, No. 10 aluminum lakes of yellow, Sunset yellow aluminum lake, indigo aluminum lake.
Coating method：Coating powder is prepared into certain density film coating liquid (solid content is 10~20%) with purified water, to pressure
The tablet of system is coated in BGB-5F high-efficiency coating machines, seed-coating machine EAT：55-60 DEG C, 38-45 DEG C of leaving air temp, main frame
Rotating speed：5-10r/min；Not timing weighs the piece weight of 10 slice, thin pieces, during coating weight gain about 4%, stops being coated.
Embodiment 7
By in embodiment 6, with " being coated the Film coated tablets after 6-1 " is coated and carry out aluminium-plastic bubble plate packing, with " being coated 6-2 " coatings
Film coated tablets afterwards carries out aluminium-plastic bubble plate packing, with " Film coated tablets after coating 6-3 " is coated carries out aluminium-plastic bubble plate packing.
A is organized in table 2 and " is coated 6-1 ", group B " is coated 6-2 ", group C is aluminium for aluminium-plastic bubble plate packing for aluminium-plastic bubble plate packing
Mould " being coated 6-1 " and be packaged in again in closed aluminium foil packaging bag for blister package.By 3 set products in 92.5% relative humidity, 25 DEG C
Under the conditions of investigate its stability, the results are shown in Table shown in 2.As a result show：Can preferably it prevent containing polyvinyl alcohol in coating material
Tide, sample is placed under conditions of high humidity, and stability is more preferable.
Table 2
| Project | Group A | Group B | Group C |
| It is maximum single miscellaneous | 0.72% | 0.56% | 0.34% |
| It is total miscellaneous | 1.11% | 0.84% | 0.68% |
| Impurity R-11 | 0.06% | Do not detect | Do not detect |
| Optical isomer | 0.16% | Do not detect | Do not detect |
In table 3 organize D be aluminium-plastic bubble plate packing or it is packless " be coated 6-2 ", group E be aluminium-plastic bubble plate packing or it is packless " bag
Clothing 6-3 "；Two set products are investigated its stability, the results are shown in Table shown in 3 in 40 DEG C ± 2 DEG C under the conditions of RH75% ± 5%.
Table 3
Claims (10)
1. a kind of pharmaceutical composition containing Ramosetron or its pharmaceutically-acceptable salts, it is characterised in that the composition is piece
Dosage form formula, the tablet is made up of label with coating, the label by Ramosetron or its pharmaceutically-acceptable salts, stabilizer,
Filler, disintegrant, adhesive, label lubricant composition, the coating include polyvinyl alcohol, polyethylene glycol, titanium dioxide
Titanium.
2. pharmaceutical composition according to claim 1, it is characterised in that in the label every containing Ramosetron or its
0.002~0.006mg of pharmaceutically-acceptable salts；
It is preferred that the Ramosetron pharmaceutically-acceptable salts be Ramosetron HCl；
Preferably contain 0.002~0.006mg of Ramosetron HCl.
3. pharmaceutical composition according to claim 1, it is characterised in that the stabilizer be selected from citric acid, citric anhydride,
Tartaric acid, malic acid；
It is preferred that the stabilizer be citric acid；
It is preferred that the stabilizer and Ramosetron or the mass ratio of its pharmaceutically-acceptable salts be (48~200)：1.
4. pharmaceutical composition according to claim 1, it is characterised in that the filler be selected from lactose, microcrystalline cellulose,
Mannitol；
It is preferred that the filler be microcrystalline cellulose；
It is preferred that the filler be that microcrystalline cellulose is Avicel PH-302 or Avicel PH-200；
It is preferred that the filler and Ramosetron or the mass ratio of its pharmaceutically-acceptable salts be (17000~27000)：1.
5. pharmaceutical composition according to claim 1, it is characterised in that the disintegrant is selected from carboxymethyl cellulose, carboxylic
Methylcellulose calcium, sodium carboxymethylcellulose, Ac-Di-Sol, low-substituted hydroxypropyl cellulose, PVPP；
It is preferred that the disintegrant be selected from low-substituted hydroxypropyl cellulose；
It is preferred that the disintegrant and filler mass ratio be (6.5~16)：100.
6. pharmaceutical composition according to claim 1, it is characterised in that described adhesive is selected from hydroxypropyl methylcellulose, hydroxyl
Third cellulose, PVP；
It is preferred that described adhesive be hydroxypropylcellulose；
It is preferred that described adhesive and filler mass ratio be (2~3.5)：100.
7. pharmaceutical composition according to claim 1, it is characterised in that the label lubricant is selected from magnesium stearate, hard
Resin acid calcium, stearic acid, talcum powder；
It is preferred that the label lubricant be magnesium stearate；
It is preferred that the label lubricant and filler mass ratio be (0.4~0.75)：100.
8. according to pharmaceutical composition according to any one of claims 1 to 7, it is characterised in that the quality of the coating is label
The 3%~5% of quality.
9. according to pharmaceutical composition according to any one of claims 1 to 7, it is characterised in that also include being coated in the coating
Lubricant；
It is preferred that the coating lubricant be selected from magnesium stearate, calcium stearate, stearic acid, talcum powder；
It is preferred that the coating lubricant be talcum powder；
It is preferred that the polyvinyl alcohol, polyethylene glycol, titanium dioxide, be coated lubricant mass ratio be (30~60)：(2~10)：
(5~20)：(5~20).
10. according to pharmaceutical composition according to any one of claims 1 to 7, it is characterised in that also include in the coating
Toner.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610178048.0A CN107224430A (en) | 2016-03-25 | 2016-03-25 | A kind of pharmaceutical composition of hydrochloric Ramosetron |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610178048.0A CN107224430A (en) | 2016-03-25 | 2016-03-25 | A kind of pharmaceutical composition of hydrochloric Ramosetron |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109115914A (en) * | 2018-10-03 | 2019-01-01 | 淮安安莱生物科技有限公司 | A kind of efficient liquid-phase chromatography method separating Ramosetron HCl and its S type enantiomter |
| CN109115913A (en) * | 2018-10-03 | 2019-01-01 | 淮安安莱生物科技有限公司 | A kind of HPLC method based on conventional phenyl chromatography post separation Ramosetron HCl He its S type enantiomter |
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| CN1723021A (en) * | 2003-01-31 | 2006-01-18 | 山之内制药株式会社 | Stable solid medicinal composition for oral administration. |
| CN104523690A (en) * | 2015-02-08 | 2015-04-22 | 长沙佰顺生物科技有限公司 | Topiroxostat oral preparation and preparation method thereof |
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- 2016-03-25 CN CN201610178048.0A patent/CN107224430A/en active Pending
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| CN1723021A (en) * | 2003-01-31 | 2006-01-18 | 山之内制药株式会社 | Stable solid medicinal composition for oral administration. |
| CN104523690A (en) * | 2015-02-08 | 2015-04-22 | 长沙佰顺生物科技有限公司 | Topiroxostat oral preparation and preparation method thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109115914A (en) * | 2018-10-03 | 2019-01-01 | 淮安安莱生物科技有限公司 | A kind of efficient liquid-phase chromatography method separating Ramosetron HCl and its S type enantiomter |
| CN109115913A (en) * | 2018-10-03 | 2019-01-01 | 淮安安莱生物科技有限公司 | A kind of HPLC method based on conventional phenyl chromatography post separation Ramosetron HCl He its S type enantiomter |
| CN109115914B (en) * | 2018-10-03 | 2021-06-04 | 四川中科微纳科技有限公司 | High performance liquid chromatography method for separating ramosetron hydrochloride and S-type enantiomer thereof |
| CN109115913B (en) * | 2018-10-03 | 2021-08-06 | 济南迪安医学检验中心有限公司 | HPLC method for separating ramosetron hydrochloride and S-type enantiomer thereof based on conventional phenyl chromatographic column |
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Address after: 211112 Kejian Road 699, Jiangning District, Nanjing City, Jiangsu Province Applicant after: Jiangsu Aosaikang Pharmaceutical Co., Ltd. Address before: 211112 Kejian Road 699, Jiangning District, Nanjing City, Jiangsu Province Applicant before: Jiangsu Aosaikang Pharmaceutical Co., Ltd. |
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Application publication date: 20171003 |