CN104586814A - Aprepitant capsules - Google Patents
Aprepitant capsules Download PDFInfo
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- CN104586814A CN104586814A CN201510058515.1A CN201510058515A CN104586814A CN 104586814 A CN104586814 A CN 104586814A CN 201510058515 A CN201510058515 A CN 201510058515A CN 104586814 A CN104586814 A CN 104586814A
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- aprepitant
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Abstract
The invention belongs to the technical field of medicines, and specifically relates to aprepitant capsules. The aprepitant capsules contain aprepitant, hydroxy propyl cellulose, diethylene glycol monoethyl ether, fumed silica and other pharmaceutically acceptable filler, disintegrant and lubricant. A preparation method of the aprepitant capsules comprises the following steps: dissolving aprepitant in diethylene glycol monoethyl ether, adding hydroxy propyl cellulose, stirring to dissolve, adding fumed silica to adsorb, then uniformly mixing with the other pharmaceutically acceptable filler, disintegrant and lubricant, and directly filling capsules. Compared with the prior art, the aprepitant capsules disclosed by the invention are fast in medicine dissolution speed, simple in process, and free from a surfactant and a micronization treatment. An acceleration test result indicates that the prepared aprepitant capsules are high in dissolution rate.
Description
Technical field
The invention belongs to medical art, be specifically related to a kind of Aprepitant capsule.
Background technology
Aprepitant (aprepitanl) is that listing is at present for the nk 1 receptor antagonist of emesis.Nk 1 receptor is the binding site of tachykinin (NKA) Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 (SP), is positioned at brain stem vomiting center and gastrointestinal tract.Animal experiment proves that SP can bring out vomiting.And the medicine of specific inhibition this receptor can prevent allly to cause the vomiting of telling stimulus object (comprising cisplatin) and causing.Aprepitant is nk 1 receptor blocker, by combining the effect of blocking Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 with nk 1 receptor (being mainly present in central nervous system and periphery thereof).Aprepitant can pass through blood brain barrier, captures the nk 1 receptor in brain, has selectivity and high-affinity, and very low to NK-2 and NK-3 receptor affinity.Aprepitant is a unique nk 1 receptor medicine gone on the market.The complete control rate of its emesis improves 14.98% than 5-hydroxytryptamine receptor antagonist class medicine.
Aprepitant is almost insoluble in water, and when pH2 ~ 10, the dissolubility of Aprepitant in water is very low be 3 ~ 7 μ g/ml, LogP during pH 7.0 is 4.8.There is the shortcoming that dissolution velocity is slow, dissolution in vitro is low, bioavailability is low, the absorption of medicine is had a certain impact.In order to improve the dissolution of Aprepitant, generally adopt the method adding exhibiting high surface activating agent in prescription, although the method can increase the dissolution of Aprepitant, exhibiting high surface activating agent brings a large amount of toxic and side effects to human body.Thus seek a kind of nontoxic method to increase the dissolution of Aprepitant, the method improving Aprepitant bioavailability is extremely urgent.
Comparatively speaking, Aprepitant is oleophylic slightly, is slightly dissolved in ethanol and isopropyl acetate, is slightly soluble in acetonitrile, and according to Biopharmaceutics Classification (BCS), Aprepitant should belong to BCS IV class.In order to increase its water solublity, and then increasing its oral administration biaavailability, in WO2003049718, making public for the first time the nano-particle composition containing Aprepitant, wherein the surface adsorption surface stabilizer of Aprepitant, thus make particle diameter be less than 1000nm.The preparation method provided in embodiment is specially and is dispersed in liquid dispersion medium by active component Aprepitant, and under the existence of abrasive media and surface stabilizer, adopt mechanical means wet milling, reduce the mean diameter of active component, then separating obtained from abrasive media nano-composition.Although adopt wet grinding significantly can reduce mean diameter, reach hundreds of nanometer, thus increase its water solublity.CN103251556A discloses a kind of Aprepitant nanosuspension and preparation method thereof, is also to control drug particle at Nano grade.These prior aries, its preparation technology is cumbersome, such as must the nano-particle of resulting separation from abrasive media, and time consumption and energy consumption, is not easy to amplify and produces.In addition, employing wet grinding cannot produce the granule that particle diameter is less than 100 nanometers.
Patent CN102525880A provides a kind of Aprepitant solid dispersion composition and preparation method thereof, and also comprising this solid dispersion compositions to prepare further becomes pharmaceutical composition.It contains Aprepitant and at least one water-soluble polymer, and Aprepitant is dispersed in water-soluble polymer.This invention adopts hot-melt extruded legal system for solid dispersion, have considerable influence, and from this working of an invention effect, 15min is stripping about 83% only to medicine stability, not stripping completely.
Prior art all fails to provide a kind of dissolution high, the simple Aprepitant preparation of preparation technology.
Summary of the invention
For the deficiencies in the prior art, the invention provides a kind of Aprepitant capsule and preparation method thereof.Solid dispersions technique is combined with solubilizing agent and adsorbent by inventor, first solid dispersion solubilize drugs is prepared, the dispersion solution aerosil of medicine is adsorbed, mix homogeneously with pharmaceutically acceptable adjuvant again, the direct filled capsules of powder, the stripping of gained preparation is rapid, and preparation technology is simple.
Specifically, the present invention is achieved through the following technical solutions:
The invention provides a kind of Aprepitant capsule, containing Aprepitant, hydroxypropyl cellulose, TC, aerosil and other pharmaceutically acceptable filler, disintegrating agent, lubricant.Described Aprepitant capsule, the weight ratio of Aprepitant and TC is 1:3 ~ 5; Preferably, weight ratio is 1:3.
Described Aprepitant capsule is prepared from by the following method: Aprepitant is dissolved in TC, adds hydroxypropyl cellulose, is stirred to dissolve; Add aerosil absorption again, then pharmaceutically acceptable filler, disintegrating agent, mix lubricant are even with other, capsule charge.
Described Aprepitant capsule, the weight ratio of Aprepitant and hydroxypropyl cellulose is 1:1 ~ 3.Preferably, weight ratio is 1:2.
Described Aprepitant capsule, the weight ratio of Aprepitant and aerosil is 1:18 ~ 28.Preferably, weight ratio is 1:24.
Described filler be selected from microcrystalline Cellulose, lactose, mannitol, starch, dextrin one or more.
Described disintegrating agent be selected from carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose one or more.
Described lubricant be selected from magnesium stearate, sodium stearyl fumarate, Pulvis Talci, silicon dioxide one or more.
Compared with prior art, drug-eluting speed is fast in the present invention, and technique is simple, does not need to add surfactant, does not also need micronization processes.Accelerated test result shows, Aprepitant capsule dissolubility prepared by the present invention is better.
Detailed description of the invention
Following examples further describe beneficial effect of the present invention, embodiment is only for the object of illustration, do not limit the scope of the invention, the simultaneously apparent change made according to the present invention of those of ordinary skill in the art and modification are also contained within the scope of the invention.
Embodiment 1
Preparation technology:
Aprepitant is dissolved in TC, adds hydroxypropyl cellulose, is stirred to dissolve, then adds the aerosil absorption of recipe quantity, then with lactose, carboxymethyl starch sodium, magnesium stearate mix homogeneously, adopts direct capsule charge to form.
Embodiment 2
Preparation technology:
Aprepitant is dissolved in TC, add hydroxypropyl cellulose, be stirred to dissolve, then add the aerosil absorption of recipe quantity, then with microcrystalline Cellulose, polyvinylpolypyrrolidone, magnesium stearate mix homogeneously, direct capsule charge is adopted to form.
Embodiment 3
Preparation technology:
Aprepitant is dissolved in TC, add hydroxypropyl cellulose, be stirred to dissolve, then add the aerosil absorption of recipe quantity, then with microcrystalline Cellulose, polyvinylpolypyrrolidone, magnesium stearate mix homogeneously, direct capsule charge is adopted to form.
Embodiment 4
Preparation technology:
Aprepitant comminution by gas stream, particle diameter is D90=10.8 μm, add the hydroxypropyl cellulose of recipe quantity, aerosil, microcrystalline Cellulose, polyvinylpolypyrrolidone mix homogeneously, add TC, granulate, then add magnesium stearate, mix homogeneously, adopt direct capsule charge to form.
Embodiment 5
Preparation technology:
Aprepitant is dissolved in TC, add hydroxypropyl cellulose, be stirred to dissolve, then add the aerosil absorption of recipe quantity, then with microcrystalline Cellulose, polyvinylpolypyrrolidone, magnesium stearate mix homogeneously, direct capsule charge is adopted to form.
Embodiment 6
Preparation technology:
Aprepitant is dissolved in TC, add hydroxypropyl cellulose, be stirred to dissolve, then add the aerosil absorption of recipe quantity, then with microcrystalline Cellulose, polyvinylpolypyrrolidone, magnesium stearate mix homogeneously, direct capsule charge is adopted to form.
Embodiment 7
Preparation technology:
Take Aprepitant and the microcrystalline Cellulose mix homogeneously of recipe quantity.Aprepitant microcrystalline cellulose mixt is added in pulverizer and pulverizes 3 minutes, then with aerosil, hydroxypropyl cellulose, the polyvinylpolypyrrolidone of recipe quantity, mix homogeneously, add TC, granulate, then magnesium stearate is added, mix homogeneously, adopts direct capsule charge to form.
Comparative example 1
Preparation technology:
Aprepitant is dissolved in TC, then adds the aerosil absorption of recipe quantity, then with microcrystalline Cellulose, polyvinylpolypyrrolidone, magnesium stearate mix homogeneously, adopts direct capsule charge to form.
Comparative example 2
Preparation technology:
Aprepitant comminution by gas stream, D90=10.3 μm, then with microcrystalline Cellulose, polyvinylpolypyrrolidone, magnesium stearate mix homogeneously, adopts direct capsule charge to form.
Checking embodiment
Dissolution determination: adopt the dissolution of high performance liquid chromatography to Aprepitant capsule to measure, chromatographic condition is identical with determination, uses octadecylsilane chemically bonded silica chromatographic column; With water: acetonitrile (40:60) is mobile phase; Flow velocity is 1.0ml per minute; Determined wavelength is 210nm; By external standard method with the dissolution of Aprepitant in calculated by peak area need testing solution.The stripping quantity of this product 5min should be not less than 80% (Q) of labelled amount.
Dissolution medium: the solution of 2.2% sodium lauryl sulphate, medium volume: 900ml, rotating speed of agitator 100rpm.Stripping assay method is Chinese Pharmacopoeia version annex X C second methods in 2010 and device etc.The results detailed in Table 1.
The each embodiment measurement result of table 1
| Embodiment | 0 day result (%) | 40 DEG C, 75%RH accelerates result (%) after 6 months |
| Embodiment 1 | 98.9 | 99.0 |
| Embodiment 2 | 99.6 | 99.8 |
| Embodiment 3 | 99.6 | 98.9 |
| Embodiment 4 | 78.7 | 79.4 |
| Embodiment 5 | 81.2 | 80.8 |
| Embodiment 6 | 80.1 | 80.5 |
| Embodiment 7 | 79.3 | 80.1 |
| Comparative example 1 | 56.6 | 54.3 |
| Comparative example 2 | 65.7 | 61.3 |
As seen from the table, the embodiment of the present invention 1 ~ 3 stripping is rapid, full 5min can be molten, is no matter from the stripping result of 0 day or substantially unchanged at the stripping measurement result drug-eluting of acceleration after 6 months, the good stability of medicine; Embodiment 4 is granulated by TC, because raw material can not dissolve in a solvent fully, so from the results contrast with embodiment 1 ~ 3, the dissolution rate of medicine is slightly slow, and technique is not so good as the way of adsorbing through adjuvant after raw material is first dissolved in TC; Embodiment 5, adsorbent amount is on the high side, hinders drug-eluting, causes dissolution rate partially slow; Embodiment 6, TC consumption is few, and medicine can not fully be dissolved in wherein, and cause stripping result poor, consumption is excessive, and the adjuvant of its corresponding absorption also can increase, the appearance of the problem such as cause cost and sheet heavily; Embodiment 7, consider first raw material and partial supplementary material micronization processes to be improved the dispersion of medicine at adjuvant, and then add the preparation technology of TC granulation, the object improving stripping is reached with this, but from the result that stripping measures, the stripping of medicine increases to some extent, but DeGrain; In comparative example 1, because do not add hydroxypropyl cellulose, when stripping measures in solvent, TC and water dissolve each other, and cause solvent to be dispersed in water rapidly, cause medicine to separate out, therefore undesirable from stripping measurement result stripping result, stripping is unhappy; And in comparative example 2, preparation technology be raw material through micronization processes, accelerating stripping from reducing the particle diameter of medicine merely, belonging to the method for conventional increase drug-eluting, from the stripping of stripping determination data, comparatively the present invention is slow.
Claims (9)
1. an Aprepitant capsule, is characterized in that, containing Aprepitant, hydroxypropyl cellulose, TC, aerosil and other pharmaceutically acceptable filler, disintegrating agent, lubricant; The weight ratio of described Aprepitant and TC is 1:3 ~ 5.
2. Aprepitant capsule according to claim 1, is characterized in that, the weight ratio of Aprepitant and TC is 1:3.
3. Aprepitant capsule according to claim 1, it is characterized in that, it is prepared from by the following method: Aprepitant is dissolved in TC, add hydroxypropyl cellulose, be stirred to dissolve, add aerosil absorption, then pharmaceutically acceptable filler, disintegrating agent, mix lubricant are even with other, and direct capsule charge forms.
4. Aprepitant capsule according to claim 1, is characterized in that, the weight ratio of Aprepitant and hydroxypropyl cellulose is 1:1 ~ 3.
5. Aprepitant capsule according to claim 1, is characterized in that, the weight ratio of Aprepitant and aerosil is 1:18 ~ 28.
6. Aprepitant capsule according to claim 1, is characterized in that, the weight ratio of Aprepitant and aerosil is 1:24.
7. Aprepitant capsule according to claim 1, is characterized in that, described filler be selected from microcrystalline Cellulose, lactose, mannitol, starch, dextrin one or more.
8. Aprepitant capsule according to claim 1, is characterized in that, described disintegrating agent be selected from carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose one or more.
9. Aprepitant capsule according to claim 1, is characterized in that, described lubricant be selected from magnesium stearate, sodium stearyl fumarate, Pulvis Talci, silicon dioxide one or more.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201510058515.1A CN104586814B (en) | 2015-02-04 | 2015-02-04 | A kind of Aprepitant capsule |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510058515.1A CN104586814B (en) | 2015-02-04 | 2015-02-04 | A kind of Aprepitant capsule |
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| CN104586814B CN104586814B (en) | 2017-11-10 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104865336A (en) * | 2015-06-09 | 2015-08-26 | 成都百裕科技制药有限公司 | Method for detecting related substances in aprepitant by high performance liquid chromatography |
| CN107007568A (en) * | 2017-06-01 | 2017-08-04 | 四川制药制剂有限公司 | The novel processing step of Aprepitant capsule |
| CN107260705A (en) * | 2017-06-08 | 2017-10-20 | 武汉励合生物医药科技有限公司 | A kind of preparation method of Aprepitant Nano capsule |
| CN115487194A (en) * | 2022-04-28 | 2022-12-20 | 江苏慧聚药业股份有限公司 | Aprepitant pharmaceutical composition and preparation method thereof |
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| CN101048180A (en) * | 2004-10-25 | 2007-10-03 | 日本烟草产业株式会社 | Solid formulation with improved solubility and stability, and method for producing said formulation |
| US20090209541A1 (en) * | 2006-06-16 | 2009-08-20 | Dr. Reddy's Laboratories Ltd. | Aprepitant compositions |
| CN102525880A (en) * | 2010-12-31 | 2012-07-04 | 江苏正大天晴药业股份有限公司 | Aprepitant solid dispersion composition |
| CN103251556A (en) * | 2013-05-30 | 2013-08-21 | 苏州普罗达生物科技有限公司 | Aprepitant nanosuspension and preparation method thereof |
| CN103271887A (en) * | 2013-06-07 | 2013-09-04 | 昆明振华制药厂有限公司 | Furazolidone tablet preparation method |
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2015
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| CN101048180A (en) * | 2004-10-25 | 2007-10-03 | 日本烟草产业株式会社 | Solid formulation with improved solubility and stability, and method for producing said formulation |
| US20090209541A1 (en) * | 2006-06-16 | 2009-08-20 | Dr. Reddy's Laboratories Ltd. | Aprepitant compositions |
| CN102525880A (en) * | 2010-12-31 | 2012-07-04 | 江苏正大天晴药业股份有限公司 | Aprepitant solid dispersion composition |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104865336A (en) * | 2015-06-09 | 2015-08-26 | 成都百裕科技制药有限公司 | Method for detecting related substances in aprepitant by high performance liquid chromatography |
| CN107007568A (en) * | 2017-06-01 | 2017-08-04 | 四川制药制剂有限公司 | The novel processing step of Aprepitant capsule |
| CN107260705A (en) * | 2017-06-08 | 2017-10-20 | 武汉励合生物医药科技有限公司 | A kind of preparation method of Aprepitant Nano capsule |
| CN115487194A (en) * | 2022-04-28 | 2022-12-20 | 江苏慧聚药业股份有限公司 | Aprepitant pharmaceutical composition and preparation method thereof |
| CN115487194B (en) * | 2022-04-28 | 2023-09-29 | 江苏慧聚药业股份有限公司 | Aprepitant pharmaceutical composition and preparation method thereof |
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