CN106880603A - A kind of oral disnitegration tablet containing Topiroxostat and preparation method thereof - Google Patents
A kind of oral disnitegration tablet containing Topiroxostat and preparation method thereof Download PDFInfo
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- CN106880603A CN106880603A CN201510930894.9A CN201510930894A CN106880603A CN 106880603 A CN106880603 A CN 106880603A CN 201510930894 A CN201510930894 A CN 201510930894A CN 106880603 A CN106880603 A CN 106880603A
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- Prior art keywords
- topiroxostat
- oral disnitegration
- disnitegration tablet
- preparation
- disintegrant
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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
- A61K9/0012—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
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
Abstract
The invention discloses a kind of oral disnitegration tablet containing Topiroxostat and preparation method thereof, belong to pharmaceutical technology field.The oral disnitegration tablet contains Topiroxostat, hydrophilic filler, water-soluble binder, disintegrant, lubricant and flavouring etc., its preparation process is simple, it is convenient to take, rapid-action, up to peak is early, curative effect is obvious.
Description
Technical field
The present invention relates to the oral disnitegration tablet that can be disintegrated rapidly and the method for producing the formulation that a kind of active component is Topiroxostat,
Belong to field of pharmaceutical preparations.
Background technology
With the development of society, the change of dietary structure, the incidence of disease of gout shows ever-increasing trend.China is to gout
Research come from the 1950's, 1948, Chen Yueshu reported 2 gouts first.In document before 1958 only
25 reports.Shandong coastal area illness rate in 2004 is 1.14% (increased 3 times in nearly 10 years).Taiwan Province is gout high
Hair province, the illness rate of 18 aborigines' gout more than one full year of life is 11.70%.Gout also receives much concern in other developing countries.
One investigation about African rheumatic disease shows that the illness rate of whole Africa gout is increasing.Relative to developing country,
Gout is also increasingly increasing in the illness rate of developed country, and hair patient's number of European and American areas gout accounts for the 0.13%~0.37% of total population,
Annual morbidity is 0.20%0~0.35%.
Topiroxostat (Topiroxostat), chemical entitled 4- [5- (pyridin-4-yl) -1H-1,2,4- triazole -3- bases] pyridine -2- formonitrile HCNs.Its
Molecular formula is C13H8N6, molecular weight is 248.24, and its structural formula of compound is as follows：
Its trade name " TOPILORIC ".By the research and development of Japanese fuji medicine Co., Ltd. for treating gout, antihyperuricemic
The medicine of disease, gets the Green Light listing in June, 2013 in Japan.
Topiroxostat has significant inhibitory action to the XOR of oxidized form and reduced form, thus its effect for reducing uric acid it is more powerful,
Persistently, thus this product can be used for treat gout chronic hyperuricemia.Compared with allopurinol, Topiroxostat has two advantages：
1：Allopurinol only has inhibitory action to the XOR of reduced form, and Topiroxostat has aobvious to the XOR of oxidized form and reduced form
The inhibitory action of work, thus its effect for reducing uric acid is more powerful, lasting；2：Because allopurinol is purine analogue, can not
The influence for causing to be related to purine and pyridine to be metabolized other enzymatic activitys for avoiding.Therefore, it is necessary to repeat heavy dose of in allopurinol treatment
It is administered to maintain levels of drugs higher, thus also brings the serious or even fatal adverse reaction caused by drug accumulation.And
Topiroxostat is non-purines XOR inhibitor, therefore with more preferable security.
Topiroxostat oral disnitegration tablet of the invention need not use water delivery service, and saliva can be disintegrated it, mask medicine in itself
Bad smell and bitter taste, improve the compliance of patient's Long-term taking medicine, be particularly suited for the elderly, children and other swallow it is tired
Difficult patient.Oral disnitegration tablet can rapidly be disintegrated before intestines and stomach are reached and be dispersed into fine particle, disperse more equal in the gastrointestinal tract
Even, diffusional area is big, can make the rapid dissolution of medicine, quick to absorb, rapid-action.
The content of the invention
It is an object of the invention to provide the oral disnitegration tablet formulation of Topiroxostat, the technical complexity that the production of the formulation need not be very high,
This formulation considers Topiroxostat low-solubility, is fast and efficiently given birth to producing the characteristics of by the rapid disintegration of oral disnitegration tablet
Thing availability, to obtain preferable clinical efficacy.
Topiroxostat oral disnitegration tablet of the present invention, the pharmaceutical composition contains 4- [5- (pyridin-4-yl) -1H-1,2,4- tri- as follows
Azoles -3- bases] pyridine -2- formonitrile HCNs：
And hydrophilic filler, water-soluble binder, disintegrant, lubricant and flavouring；Wherein bulk drug and hydrophilicity condiment
Micronizing altogether, its ratio is 1:1-1:50(w/w)；The disintegration time for using static disintegration time mensuration method to determine is 12-60s,
Preferably 14-45s.
The hydrophilicity condiment being micronized altogether with Topiroxostat in the present invention includes mannitol, cornstarch, microcrystalline cellulose, lactose
In one kind, its ratio be 1:1-1:20 (w/w), particularly preferred 1:2-1:5(w/w).The particle diameter of Topiroxostat after being micronized altogether
Control in 1-50 μ ms, preferably in 1-30 μ ms.
The content of active component Topiroxostat is 2%-20%, preferably 10mg, 20mg in the present invention.
Hydrophilic filler in the present invention is in lactose, sucrose, mannitol, microcrystalline cellulose, starch, dextrin, sorbierite
One or more, its consumption be 30%-95%, preferably one or more in lactose, mannitol, microcrystalline cellulose, starch,
The preferred 40%-90% of its consumption.
Water-soluble binder in the present invention is one or more in PVP, hydroxypropyl cellulose, hydroxypropyl methyl cellulose,
Its consumption is 0.2%-10%, preferably 0.5%-5%.
Disintegrant in the present invention is Ac-Di-Sol, PVPP, low-substituted hydroxypropyl cellulose, carboxymethyl form sediment
One or more in powder sodium, its consumption is 2%-50%, preferably 5%-40%.
Lubricant in the present invention for the one kind in silica, talcum powder, magnesium stearate, stearic acid, sodium stearyl fumarate or
Various, its consumption is 0.1%-5%, preferably 0.5%-3%.
Flavouring in the present invention is one or more in acesulfame potassium, Aspartame, menthol, Sucralose, essence class,
Its consumption is 0.1%-20%, preferably 0.5%-10%.
Topiroxostat oral disnitegration tablet of the present invention, its piece weight 80-300mg, preferably 100-250mg；Hardness 2-7kgf,
Preferably 3-5kgf.
The advantage of the invention is that：
1) Topiroxostat oral disnitegration tablet of the invention, in preparation process, in Topiroxostat bulk drug and hydrophilic filler one
Kind or it is various carry out common micronizing, due to the hydrophilic nmature of filler, Topiroxostat with its altogether micronizing after enhance bulk drug
Dissolubility, and micronization technology effect in itself, also enhance the dissolubility of bulk drug simultaneously, improve Topiroxostat raw material
The property of medicine indissoluble.
2) it is 12-60s that Topiroxostat oral disnitegration tablet of the invention uses the disintegration time that static disintegration time mensuration method is determined,
Preferably 14-45s.Disintegration is rapid, has exceeded the disintegration time limited of oral disnitegration tablet in the prior art, for Clinical practice provide it is fast
The Topiroxostat oral disnitegration tablet of speed disintegration.
3) Topiroxostat oral disnitegration tablet of the invention need not use water delivery service, and saliva can be disintegrated it, mask medicine in itself
Bad smell and bitter taste, improve the compliance of patient's Long-term taking medicine, be particularly suited for the elderly, children and other swallow
Difficult patient.Oral disnitegration tablet can rapidly be disintegrated before intestines and stomach are reached and be dispersed into fine particle, disperse in the gastrointestinal tract more
Uniformly, diffusional area is big, can make the rapid dissolution of medicine, quick to absorb, rapid-action.
Specific embodiment
Further present disclosure is described in further detail with embodiment below.But this should not be interpreted as this hair
It is bright to be limited by specific embodiment.All technologies realized based on the above of the invention belong to the scope of the present invention.
Embodiment 1
Preparation technology：
(1) Topiroxostat and mannitol are total to micronization processes in proportion；
(2) Topiroxostat of recipe quantity is well mixed with mannitol, microcrystalline cellulose, sodium carboxymethyl starch in blender；
(3) to the wet softwood of hydroxypropylcellulose aqueous solution system that 4% is added in said mixture, granulation；
(4) above-mentioned particle drying converts the use of additional magnesium stearate, Mint Essence and Aspartame to moisture ＜ 3% after whole grain
Amount, is well mixed with dried particle；
(5) total mixed rear granule content is determined, piece weight is converted, hardness 3-5kgf compressing tablets are controlled.It is prepared into 1000.
Embodiment 2
Preparation technology：
(1) Topiroxostat and lactose are total to micronization processes in proportion；
(2) Topiroxostat of recipe quantity is well mixed with lactose, microcrystalline cellulose, sodium carboxymethyl starch in blender；
(3) to the wet softwood of hydroxypropylcellulose aqueous solution system that 4% is added in said mixture, granulation；
(4) above-mentioned particle drying converts the use of additional magnesium stearate, Mint Essence and Aspartame to moisture ＜ 3% after whole grain
Amount, is well mixed with dried particle；
(5) total mixed rear granule content is determined, piece weight is converted, hardness 3-5kgf compressing tablets are controlled.It is prepared into 1000.
Embodiment 3
Preparation technology：
(1) Topiroxostat and lactose are total to micronization processes in proportion；
(2) Topiroxostat of recipe quantity is well mixed with lactose, mannitol, Ac-Di-Sol in blender；
(3) to the wet softwood of PVP aqueous solution system that 3% is added in said mixture, granulation；
(4) above-mentioned particle drying converts the use of additional magnesium stearate, Mint Essence and Aspartame to moisture ＜ 3% after whole grain
Amount, is well mixed with dried particle；
(5) total mixed rear granule content is determined, piece weight is converted, hardness 3-5kgf compressing tablets are controlled.It is prepared into 1000.
Embodiment 4
Preparation technology：
(1) Topiroxostat and mannitol are total to micronization processes in proportion；
(2) Topiroxostat of recipe quantity is well mixed with mannitol, microcrystalline cellulose, sodium carboxymethyl starch in blender；
(3) to the wet softwood of hydroxypropylcellulose aqueous solution system that 4% is added in said mixture, granulation；
(4) above-mentioned particle drying converts the use of additional magnesium stearate, Mint Essence and Aspartame to moisture ＜ 3% after whole grain
Amount, is well mixed with dried particle；
(5) total mixed rear granule content is determined, piece weight is converted, hardness 3-5kgf compressing tablets are controlled.It is prepared into 1000.
2nd, quality assessment method
The disintegration time limited of oral disnitegration tablet checks
Take 2mL water (37 DEG C) to be placed in 5mL test tubes, add Topiroxostat oral disintegrating tablet, start timing, opened to complete disintegration
Into independent fine particle, stop, recording disintegration time, test tube should not be moved in disintegrating procedue, 6 are taken every time and is detected,
Take its average value.
Tablet friability is checked
According to《Chinese Pharmacopoeia》Method is detected that calculating subtracts under " tablet friability inspection technique " item in 2015 editions four 0923
Weight loss (%), and seen whether the abnormal conditions such as fracture, cracking and/or crushing.
Orally disintegrating is tested and mouthfeel inspection
Healthy volunteer 6 is chosen, oral disnitegration tablet is placed in and is started timing on lingual surface, stopped to during complete disintegration in the oral cavity
Timing, records disintegration time, and oneself is placed in mouth the intraoral sensation to after being disintegrated completely to experience slice, thin piece.
The Topiroxostat oral disnitegration tablet experimental result of table 1
3rd, evaluation result
Can be disintegrated rapidly using prescription of the present invention and the Topiroxostat oral disnitegration tablet of preparation by being known with upper table, sample hardness is closed
Lattice, it is in good taste, without obvious sand type, and special production equipment is not needed, with low production cost, carry, store, transport
It is defeated and take convenient feature, patient's drug compliance is improve, with actual application value higher.
Claims (10)
1. a kind of oral disnitegration tablet, it is characterised in that contain Topiroxostat as follows in the oral disnitegration tablet：
Wherein also include hydrophilic filler, water-soluble binder, disintegrant, lubricant and flavouring.
2. oral disnitegration tablet according to claim 1, it is characterised in that wherein the content of Topiroxostat is 2%-20%.
3. oral disnitegration tablet according to claim 1, it is characterised in that described hydrophilic filler be lactose, sucrose,
One or more in mannitol, microcrystalline cellulose, starch, dextrin, sorbierite；Hydrophilic filler consumption is 30%-95%,
Preferably 40%-90%.
4. oral disnitegration tablet according to claim 1, it is characterised in that described water-soluble binder is PVP, hydroxyl
One or more in propyl cellulose, hydroxypropyl methyl cellulose；Water-soluble binder consumption is 0.2%-10%, preferably
0.5-5%.
5. oral disnitegration tablet according to claim 1, it is characterised in that described disintegrant is cross-linked carboxymethyl cellulose
One or more in sodium, PVPP, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch；Disintegrant consumption is 2%-50%
Preferably 5-40%.
6. oral disnitegration tablet according to claim 1, it is characterised in that described lubricant be silica, talcum powder,
One or more in magnesium stearate, stearic acid, sodium stearyl fumarate；Lubricant quantity is 0.1%-5%, preferably 0.5%-3%.
7. oral disnitegration tablet according to claim 1, it is characterised in that described flavouring be acesulfame potassium, Aspartame,
One or more in menthol, Sucralose, essence class；Flavouring consumption is 0.1%-20%, preferably 0.5%-10%.
8. the preparation method of oral disnitegration tablet described in claim 1, comprises the following steps：
(1) one or more in Topiroxostat and hydrophilic filler is carried out into common micronizing；
(2) Topiroxostat, hydrophilic filler, disintegrant are well mixed；
(3) to the wet softwood of aqueous solution system that water-soluble binder is added in said mixture, granulation；
(4) above-mentioned particle drying, whole grain, additional lubricant, flavouring are well mixed with dried particle；
(5) compressing tablet.
9. preparation method according to claim 8, it is characterised in that in preparation process, Topiroxostat bulk drug with it is hydrophilic
Property filler in carry out common micronizing one or more, its ratio is 1:1-1:20 (w/w), preferably 1:2-1:5(w/w).
10. preparation method according to claim 9, it is characterised in that the particle diameter of Topiroxostat 90% exists after micronizing altogether
In 1-50 μ ms, preferably in 1-30 μ ms.
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| CN201510930894.9A CN106880603A (en) | 2015-12-15 | 2015-12-15 | A kind of oral disnitegration tablet containing Topiroxostat and preparation method thereof |
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| CN201510930894.9A CN106880603A (en) | 2015-12-15 | 2015-12-15 | A kind of oral disnitegration tablet containing Topiroxostat and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109498577A (en) * | 2018-12-24 | 2019-03-22 | 宜昌三峡制药有限公司 | Ease of solubility Compound Sulfachorpyrdazine Sodium Powder |
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| 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 |
| CN104523633A (en) * | 2015-02-08 | 2015-04-22 | 长沙佰顺生物科技有限公司 | Topiroxostat dispersible tablets and preparation method of topiroxostat dispersible tablets |
| CN104758263A (en) * | 2015-04-22 | 2015-07-08 | 青岛正大海尔制药有限公司 | Topiroxostat tablet and preparation method thereof |
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- 2015-12-15 CN CN201510930894.9A patent/CN106880603A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN104523633A (en) * | 2015-02-08 | 2015-04-22 | 长沙佰顺生物科技有限公司 | Topiroxostat dispersible tablets and preparation method of topiroxostat dispersible tablets |
| CN104758263A (en) * | 2015-04-22 | 2015-07-08 | 青岛正大海尔制药有限公司 | Topiroxostat tablet and preparation method thereof |
Non-Patent Citations (1)
| Title |
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| 陈卫卫等: "《药剂学》", 31 January 2014 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109498577A (en) * | 2018-12-24 | 2019-03-22 | 宜昌三峡制药有限公司 | Ease of solubility Compound Sulfachorpyrdazine Sodium Powder |
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Application publication date: 20170623 |