CN105456209A - Topiroxostat tablet and preparation method thereof - Google Patents
Topiroxostat tablet and preparation method thereof Download PDFInfo
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- CN105456209A CN105456209A CN201510077230.2A CN201510077230A CN105456209A CN 105456209 A CN105456209 A CN 105456209A CN 201510077230 A CN201510077230 A CN 201510077230A CN 105456209 A CN105456209 A CN 105456209A
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Abstract
The invention relates to a topiroxostat tablet. The topiroxostat tablet is prepared from, by weight, 5%-60% of raw material topiroxostat, 10%-80% of auxiliary material filler, 1%-30% of disintegrating agent, 0.1%-5% of bonding agent and 0.2%-5% of lubricating agent. The topiroxostat tablet has the advantages that the topiroxostat tablet is prepared by adding an appropriate amount of the auxiliary material to the topiroxostat subjected to air jet pulverization, the drug content uniformity is good, dissolution is rapid and safe, the quality is stable, the topiroxostat tablet is suitable for industrial production, and the bioavailability is improved, so that the curative effect is improved, and the topiroxostat tablet is convenient to store and use.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specially and relate to a kind of preparation method containing holder his tablet of department.
Background technology
Gout is the crystal dependency arthrosis caused by monosodium urate salt (MSU) deposits, directly related with the hyperuricemia caused by purine metabolic disturbance and (or) underexcretion, refer in particular to acute characteristic arthritis and chronic gout stone disease, mainly comprising acute attack arthritis, tophus formation, tophaceous chronic arthritis, urate nephropathy and uric acid lithangiuria, can there is joint deformity and renal insufficiency in severe one.Gout often accompanies the performances such as abdominal obesity, hyperlipemia, hypertension, type 2 diabetes mellitus and cardiovascular diseases.
For the treatment of gout, current clinical mainstay is allopurinol, allopurinol is purine analogue, affect purine and other enzymatic activitys of pyridine metabolism, in the treatment, need to repeat heavy dose of administration to maintain higher levels of drugs, serious untoward reaction can be produced because dosage great Yi causes medicine body accumulation.And he is that the XOR of non-purines XOR inhibitor to oxidized form and reduced form all has significant inhibitory action to hold in the palm a department, thus its effect reducing uric acid is more powerful, lasting, and cardiovascular system is had no adverse effects, there is better safety, significantly comparatively allopurinol is good in clinical efficacy performance, significantly can reduce serum uric acid level, better tolerance and untoward reaction is little, treatment hyperuricemia and gout have great application prospect.
His raw material and tablet are taken charge of in holder, it is the new product that Shanghai Mai Bu Pharmaceutical Technology Co., Ltd independently researchs and develops, novel high selectivity, reversibility xanthine oxidase inhibitor, gout and high hematuria acid disease is used in Japan's approval listing on June 28th, 2013, trade name: TOPILORIC, this kind is gone on the market not yet at home.
Chinese invention patent CN201410260589 discloses a kind of stable holder his sheet of department and preparation method thereof, and concrete preparation method is powder vertical compression.But its crude drug accounts for preparation proportion comparatively large (29%), nearly 30%.Crude drug is water-soluble hardly, needs pulverization process to improve stripping, but poor fluidity after raw material pulverizing, particle diameter is little.Be difficult to after mixing with other adjuvant ensure mobility, and because of supplementary material particle diameter difference large, be easy to deposit and layering in tableting processes at midbody particle.And powder vertical compression to equipment and adjuvant dependency high, dust is large.Domestic equipment adjuvant is in this regard also ripe far away at present, and is not suitable for suitability for industrialized production.
He is water-soluble hardly in a holder department, and how to improve the dissolution of preparation, then improve its bioavailability, improving curative effect, is a major challenge.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art, provide that a kind of formulation ingredients is few, adjuvant is simple and easy to get, stripping is complete, stay-in-grade Febustat tablet.
For the problems referred to above, the invention provides that a kind of prescription component is few, adjuvant is conventional and tool legitimate origin, stripping is complete, his tablet of a stay-in-grade holder department.
For this reason, his tablet of the holder that provides an in the present invention department, comprises following component according to weight percent content: a holder department he 5% ~ 60%, filler 10% ~ 80%, disintegrating agent 1% ~ 30%, binding agent 0.1% ~ 5%, lubricant 0.2% ~ 5%.His tablet is taken charge of in holder prepared by the present invention, according to the character of holder his crude drug of department, by adopting super-disintegrant in rational proportion, the particle diameter (micronization crude drug) simultaneously reducing crude drug, to promote the stripping of insoluble drug, improves its bioavailability.
A kind of easy to prepare, mobility of particle and compressibility good, plain sheet smooth in appearance, rounding, color and luster are homogeneous, and hardness and friability are all better, finished product stability good containing holder his preparation of department and preparation method thereof.
Meanwhile, additionally provide the preparation method of a kind of above-mentioned holder his tablet of department in the present invention, comprise the following steps:
(1) his comminution by gas stream of department will to be held in the palm, will control its particle diameter D90 below 50 μm;
(2) by the department of the holder after pulverizing, he mixs homogeneously with filler, partial disintegration agent;
(3) add binding agent soft material, cross 16 ~ 30 mesh sieves and granulate;
(4) 60 DEG C are dried to pellet moisture is 0.5% ~ 4.0%;
(5) granule after above-mentioned drying is crossed 16 ~ 30 mesh sieve granulate;
(6) lubricant and residue disintegrating agent is added, mix homogeneously;
(7) rotary tablet press.
In the present invention, the disintegrating agent consumption in step (2) is 30% ~ 90%.
Beneficial effect:
The present invention adopts micronization (comminution by gas stream) to hold in the palm a Si Tafa, can make mixing, and granulate and carry out smoothly, production efficiency is high, and it is all comparatively outstanding to obtain outward appearance, hardness, disintegration, dissolution, stay-in-grade product.
Present invention process is stablized controlled, and feasibility is high, is more applicable to production and the clinical practice of holder his sheet of department.
Accompanying drawing explanation
Fig. 1 is that his sheet stripping correlation curve figure is taken charge of in the holder of the embodiment of the present invention 1 to 4;
Detailed description of the invention
Below in conjunction with Figure of description, the present invention will be further described.
For the problems referred to above that prior art exists, investigate through a large amount of prescription screenings and technique, the invention provides a kind of holder his preparation of department and preparation method thereof.Holder his preparation of department consists of holder his (percentage by weight is 25% ~ 35%), filler (2 kinds of filleies, weight percent of total is 60% ~ 70%) of department, disintegrating agent (percentage by weight is 1% ~ 3%), binding agent (percentage by weight is 2% ~ 4%), lubricant (percentage by weight is 0.25% ~ 1%).Preparation method is that micronization holder takes charge of him, the method for wet granulation after mixing with adjuvant, has prepared a kind of oral solid formulation taking charge of him containing holder.The powder size of inventive compound is little, mobility of particle and compressibility good, plain sheet smooth in appearance, rounding, color and luster are homogeneous, and hardness and dissolution are all better, and finished product stability is good.Formulation and technology of the present invention is stablized controlled, is applicable to suitability for industrialized production, therefore has the feasibility of height, effectively can fill up this kind market vacancy at home.
The present invention is by studying holder his preparation of department, his Task-size Controlling of department will to be ask in certain limit, him is taken charge of by micronization processes holder, micronized mode can adopt comminution by gas stream, adopt conventional wet granulation technology, qualified plain sheet sample can being prepared, not having bibliographical information to take charge of his sheet by adopting wet granulation to prepare holder after holder his micronization processes of department.
The present invention, by reducing the particle diameter of crude drug (holder takes charge of him), drastically increases the dissolution of plain sheet.Present invention process is stablized controlled, and feasibility is high, is more applicable to production and the clinical practice of holder his sheet of department.
Below by specific embodiment, the present invention is described, below in an example, the various process and methods do not described in detail are conventional methods as known in the art.Should correct understanding: embodiments of the invention are to illustrate that the present invention makes, instead of limitation of the present invention, so also belong to scope of the present invention to simple transformation of the present invention under method prerequisite of the present invention.
Embodiment 1:
Specification: 20mg
| Composition | Consumption (mg/ sheet) |
| Holder takes charge of him | 20 |
| Lactose | 34.5 |
| Microcrystalline Cellulose | 11.5 |
| Cross-linking sodium carboxymethyl cellulose | 1.4 |
| Hyprolose | 2.1 |
| Magnesium stearate | 0.35 |
| Sheet weight | 70 |
A concrete technology: his comminution by gas stream of department will to be held in the palm; control air pressure is 0.3 ~ 0.8MPa; its particle diameter D90 is made to be less than 50 μm; by micronized holder department, he takes by recipe quantity, and mixed 30 mesh sieves in wet granulator with the cross-linking sodium carboxymethyl cellulose of the lactose of recipe quantity, microcrystalline Cellulose and 1/2 recipe quantity, 600rpm stirs 10 minutes; add 5% hyprolose aqueous solution; stir 600rpm, shear 2000rpm, granulate 2 minutes.Crossing 24 mesh sieves wets whole, and 60 DEG C are dried to moisture is 0.5% ~ 4.0%, crosses 20 mesh sieve granulate.Add the magnesium stearate of recipe quantity and the cross-linking sodium carboxymethyl cellulose of 1/2 recipe quantity, in three-dimensional mixer, mix 5 minutes.With 6mm circular die tabletting.
Embodiment 2:
Specification: 40mg
| Composition | Consumption (mg/ sheet) |
| Holder takes charge of him | 40 |
| Lactose | 69 |
| Microcrystalline Cellulose | 23 |
| Cross-linking sodium carboxymethyl cellulose | 2.8 |
| Hyprolose | 4.2 |
| Magnesium stearate | 0.7 |
| Sheet weight | 140 |
A concrete technology: his comminution by gas stream of department will to be held in the palm; control air pressure is 0.3 ~ 0.8MPa; its particle diameter D90 is made to be less than 50 μm; by micronized holder department, he takes by recipe quantity, and mixed 30 mesh sieves in wet granulator with the cross-linking sodium carboxymethyl cellulose of the lactose of recipe quantity, microcrystalline Cellulose and 1/2 recipe quantity, 600rpm stirs 10 minutes; add 5% hyprolose aqueous solution; stir 600rpm, shear 2000rpm, granulate 2 minutes.Crossing 24 mesh sieves wets whole, and 60 DEG C are dried to moisture is 0.5% ~ 4.0%, crosses 20 mesh sieve granulate.Add the magnesium stearate of recipe quantity and the cross-linking sodium carboxymethyl cellulose of 1/2 recipe quantity, in three-dimensional mixer, mix 5 minutes.With 7mm circular die tabletting.
Embodiment 3:
Specification: 60mg
| Composition | Consumption (mg/ sheet) |
| Holder takes charge of him | 60 |
| Lactose | 103.5 |
| Microcrystalline Cellulose | 34.5 |
| Cross-linking sodium carboxymethyl cellulose | 4.2 |
| Hyprolose | 6.3 |
| Magnesium stearate | 1.1 |
| Sheet weight | 210 |
A concrete technology: his comminution by gas stream of department will to be held in the palm; control air pressure is 0.3 ~ 0.8MPa; its particle diameter D90 is made to be less than 50 μm; by micronized holder department, he takes by recipe quantity, and mixed 30 mesh sieves in wet granulator with the cross-linking sodium carboxymethyl cellulose of the lactose of recipe quantity, microcrystalline Cellulose and 1/2 recipe quantity, 600rpm stirs 10 minutes; add 5% hyprolose aqueous solution; stir 600rpm, shear 2000rpm, granulate 2 minutes.Crossing 24 mesh sieves wets whole, and 60 DEG C are dried to moisture is 0.5% ~ 4.0%, crosses 20 mesh sieve granulate.Add the magnesium stearate of recipe quantity and the cross-linking sodium carboxymethyl cellulose of 1/2 recipe quantity, in three-dimensional mixer, mix 5 minutes.With 8mm circular die tabletting.
Reference examples 1
Specification: 20mg
| Composition | Consumption (mg/ sheet) |
| Holder takes charge of him | 20 |
| Pregelatinized Starch | 15.0 |
| Microcrystalline Cellulose | 31.0 |
| Carboxymethylstach sodium | 1.4 |
| Hyprolose | 1.9 |
| Magnesium stearate | 0.35 |
| Sheet weight | 70 |
Concrete technology: holder department he and each adjuvant are crossed 100 mesh sieves; by recipe quantity take successively a holder department he, pregelatinized Starch, microcrystalline Cellulose and carboxymethylstach sodium; add in wet granulator; 600rpm stirs 10 minutes; add 5% hyprolose aqueous solution; stir 600rpm, shear 2000rpm, granulate 2 minutes.Crossing 24 mesh sieves wets whole, and 60 DEG C are dried to moisture is 0.5% ~ 4.0%, crosses 20 mesh sieve granulate.Add the magnesium stearate of recipe quantity, in three-dimensional mixer, mix 5 minutes.With 6mm circular die tabletting.
Note: test angle of repose uses the BT-1000 powder body tester for overall characteristic of Dandong Bai Te Instrument Ltd. to detect.
From above result, embodiment 1-3 (holder of a micronization processes department he and preferably adjuvant composition) comparatively reference examples 1 (a holder department he cross 100 mesh sieves, adjuvant composition is different from embodiment 1-3) there is better mobility of particle, element sheet outward appearance, hardness, friability and faster stripping see the above table and as shown in Figure 1.
The present invention be should be understood that; above-described embodiment; further detailed description has been carried out to object of the present invention, technical scheme and beneficial effect; these are only embodiments of the invention; be not intended to limit the present invention, every within spiritual principles of the present invention, done any amendment, equivalent replacement, improvement etc.; all should be included within protection scope of the present invention, the protection domain that protection scope of the present invention should define with claim is as the criterion.
Claims (11)
1. his sheet is taken charge of in holder, and component comprises: crude drug holder takes charge of him, and adjuvant filler, disintegrating agent, binding agent, lubricant, is characterized in that: described holder his a granularity D90 of department is less than 50 μm.
2. his sheet is taken charge of in the holder according to claims 1, and each compositions in weight percentage % counts:
Holder department him 5% ~ 60%
Filler 10% ~ 80%
Disintegrating agent 1% ~ 30%
Binding agent 0.1% ~ 5%
Lubricant 0.2% ~ 5%.
3. his sheet of holder according to claims 1 or 2 department, is characterized in that: described filler comprise in lactose, microcrystalline Cellulose and pregelatinized Starch one or more.
4. his sheet of holder according to claims 3 department, is characterized in that: described agent also comprise in mannitol, calcium hydrogen phosphate, starch, sorbitol, sucrose, dextrin, calcium sulfate one or more.
5. his sheet of holder according to claims 1 or 2 department, is characterized in that: described disintegrating agent comprise in cross-linking sodium carboxymethyl cellulose, cross-linking polyethylene pyrrolidone, low-substituted hydroxypropyl cellulose one or more.
6. his sheet of holder according to claims 5 department, is characterized in that: described disintegrating agent also comprise in carboxymethylstach sodium, starch, microcrystalline Cellulose one or more.
7. his sheet of holder according to claims 1 or 2 department, is characterized in that: described binding agent is hyprolose, polyvinylpyrrolidone, the aqueous solution of hypromellose and/or pregelatinized Starch or alcoholic solution.
8. his sheet is taken charge of in the holder according to claims 1 or 2, it is characterized in that: described lubricant is magnesium stearate, Glyceryl Behenate, sodium stearyl fumarate and/or Pulvis Talci.
9., for the preparation method of his sheet of department of the holder one of claims 1 to 8 Suo Shu, comprise the following steps:
A step 1: his comminution by gas stream of department will to be held in the palm, pulverizes and make holder his a granularity D90 of department be less than 50 μm;
Step 2: by recipe quantity weighting raw materials and adjuvant, crosses 80 or 100 mesh sieves respectively, for subsequent use;
Step 3: by the crude drug after sieving and filler and partial disintegration agent mixing, obtain mixed powder;
Step 4: add binding agent soft material;
Step 5: crushed 16 ~ 30 mesh sieves of soft material, makes wet granular;
Step 6: wet granular is placed in drying baker, 60 DEG C ± 10 DEG C are dried to pellet moisture is 0.5% ~ 4.0%;
Step 7: dry granule crosses 20 mesh sieve granulate, adds lubricant and residue disintegrating agent, mix homogeneously;
Step 8: detect midbody particle drug content, according to midbody particle content results tabletting, inner packing, finished product is examined entirely, pack, put in storage.
10. his piece preparation method is taken charge of in the holder according to claims 8, it is characterized in that: in step 3, the amount of part disintegrating agent is 30% ~ 90% of total consumption.
11. preparation methoies containing holder his preparation of department according to claim 9, is characterized in that, by the pulverizing pressure of holder his comminution by gas stream of department for pulverizing pressure 0.3 ~ 0.8MPa.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510077230.2A CN105456209A (en) | 2015-02-13 | 2015-02-13 | Topiroxostat tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510077230.2A CN105456209A (en) | 2015-02-13 | 2015-02-13 | Topiroxostat tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105456209A true CN105456209A (en) | 2016-04-06 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510077230.2A Pending CN105456209A (en) | 2015-02-13 | 2015-02-13 | Topiroxostat tablet and preparation method thereof |
Country Status (1)
| Country | Link |
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| CN (1) | CN105456209A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105919968A (en) * | 2016-06-12 | 2016-09-07 | 佛山市腾瑞医药科技有限公司 | Topiroxostat preparation and application thereof |
| CN105997906A (en) * | 2016-03-16 | 2016-10-12 | 江苏悦兴药业有限公司 | Topiroxostat tablets and preparation method thereof |
| CN106309390A (en) * | 2016-08-31 | 2017-01-11 | 安徽省润生医药股份有限公司 | Topiroxostat tablets and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101474175A (en) * | 2009-01-20 | 2009-07-08 | 重庆医药工业研究院有限责任公司 | Oral solid preparation of Febuxostat with high-bioavailability and preparation method thereof |
| CN104042577A (en) * | 2014-06-13 | 2014-09-17 | 安徽省逸欣铭医药科技有限公司 | Stable topiroxostat tablet and preparation method thereof |
| CN104230891A (en) * | 2014-08-27 | 2014-12-24 | 庄妍 | Preparation method of topiroxostat |
-
2015
- 2015-02-13 CN CN201510077230.2A patent/CN105456209A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101474175A (en) * | 2009-01-20 | 2009-07-08 | 重庆医药工业研究院有限责任公司 | Oral solid preparation of Febuxostat with high-bioavailability and preparation method thereof |
| CN104042577A (en) * | 2014-06-13 | 2014-09-17 | 安徽省逸欣铭医药科技有限公司 | Stable topiroxostat tablet and preparation method thereof |
| CN104230891A (en) * | 2014-08-27 | 2014-12-24 | 庄妍 | Preparation method of topiroxostat |
Non-Patent Citations (1)
| Title |
|---|
| TATSUO HOSOYA ETAL: "Effects of topiroxostat on the serum urate levels and urinary albumin excretion in hyperuricemic stage 3 chronic kidney disease patients with or without gout", 《CLINICAL AND EXPERIMENTAL NEPHROLOGY》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105997906A (en) * | 2016-03-16 | 2016-10-12 | 江苏悦兴药业有限公司 | Topiroxostat tablets and preparation method thereof |
| CN105919968A (en) * | 2016-06-12 | 2016-09-07 | 佛山市腾瑞医药科技有限公司 | Topiroxostat preparation and application thereof |
| CN106309390A (en) * | 2016-08-31 | 2017-01-11 | 安徽省润生医药股份有限公司 | Topiroxostat tablets and preparation method thereof |
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Application publication date: 20160406 |