CN103127011A - Roflumilast tablet and preparation method thereof - Google Patents
Roflumilast tablet and preparation method thereof Download PDFInfo
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- CN103127011A CN103127011A CN201210593342XA CN201210593342A CN103127011A CN 103127011 A CN103127011 A CN 103127011A CN 201210593342X A CN201210593342X A CN 201210593342XA CN 201210593342 A CN201210593342 A CN 201210593342A CN 103127011 A CN103127011 A CN 103127011A
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Abstract
The present invention provides a Roflumilast tablet and a preparation method of the Roflumilast tablet. The method adopts a direct powder tabletting method, production process is easy, production cycle is shortened, equipment cost and operation cost are reduced, the prepared and obtained Roflumilast tablet is good in appearance, technical process is smooth, the method possesses good operability, product dissolution rate is high, content uniformity is qualified, the Roflumilast tablet can achieve good bioavailability in human body, and therefore good curative effects is produced.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of chronic obstructive pulmonary disease (COPD) inhibitor roflumilast sheet and preparation method thereof.
Background technology
Roflumilast (Roflumilast) is by the exploitation of German Nycomed company, a new oral medicine that is used for the treatment of asthma and chronic obstructive pulmonary disease, obtained drugs approved by FDA in 2011 and be used for the treatment of chronic obstructive pulmonary disease, the listing dosage form is tablet, and commodity are by name
, specification is 0.5mg.
Roflumilast chemistry 3-(cyclo propyl methoxy) by name-N-(3,5-dichloropyridine-4-yl)-4-(difluoro-methoxy) Benzoylamide, molecular formula is C
17H
14Cl
2F
2N
2O
3, molecular weight: 403.207, structural formula is as follows:
Roflumilast with and body in active metabolite roflumilast nitrogen oxide be the selective depressant of 4 type phosphodiesterases (PDE4).Cyclic nucleotide cAMP and cGMP are important second message,second messengers in cell, comprise hormone, play an important role in the biologically that body active substance and neurotransmitter cause at various extracellular signals.Phosphodiesterase (PDE) has the function of the interior cAMP of hydrolysis cell or cGMP, makes its key enzyme that changes deactivated mononucleotide into, is the only approach of cAMP and cGMP hydrolysis.PDE4 is the main moderator of cAMP metabolism, is the main PDE isozyme of inflammation and immunocyte, is also the main PDE isozyme that is distributed in pulmonary, is a group maximum in PDE family.The roflumilast selectivity suppresses PDE4, because cAMP can cause the lax and pneumonia reaction of bronchial smooth muscle, therefore suppresses the release that PDE4 can reduce inflammatory mediator, and then suppresses the damage that lung tissue caused as respiratory tract diseases such as COPD and asthma.But roflumilast is phosphate-4 inhibitor of present unique oral medication COPD.
The roflumilast raw material be white to pale powder, hardly water-soluble and and normal hexane, slightly soluble and ethanol slightly are dissolved in acetone.Therefore, as insoluble drug, it is prepared into roflumilast the oral solid formulations such as tablet and need to solves the dissolution problem of formulation products, and need meet other tablet quality index requests such as uniformity of dosage units.
CN102274222A discloses roflumilast medicinal composition of a kind of high bioavailability and preparation method thereof, said composition is comprised of roflumilast, betacyclodextrin, lactose, microcrystalline Cellulose, magnesium stearate, adopt the method preparation of direct compression, the unexposed and former product that grinds
Stripping result contrast.Find after repetition the method, the roflumilast sheet dissolution that the method prepares and the former medicine that grinds have larger gap.
CN102743353A discloses a kind of roflumilast tablet and preparation method thereof, and the method adopts and the former product that grinds
The same drug component, i.e. roflumilast, starch, lactose, PVP through wet granulation, tabletting, obtain grinding the more consistent stripping behavior of medicine with former.
Disclosing specification in the embodiment of the CN101171005A that the former company of grinding applies for is component and the preparation method of the roflumilast sheet of 0.5mg, wherein component is roflumilast (micronization), lactose monohydrate, corn starch, polyvidoneK90, magnesium stearate adopts the bed spray drying and granulating, tabletting, the method is high to equipment requirements.
Be direct powder compression except the disclosed method of CN102274222A in said method, other is the wet granulation method of tabletting again.But the roflumilast sheet stripping result that the method for CN102274222A prepares is undesirable, and bioavailability is not high, and curative effect can't guarantee.Those skilled in the art as can be known, the dissolution of the medicine that dissolubility is little is subjected to the impact of its specific surface area and medicine finished surface character larger, very fast by the disintegration of tablet that direct powder compression prepares, after disintegrate, medicine directly discharges from powder, dispersion increases, stripping is accelerated, and relative bioavailability improves.And adopting the sheet disintegrate of wet granulation preparation slower, drug release is slower to the speed of dissolution medium.And direct powder compression (direct comPression method) directly carries out the mixture of medicine and adjuvant the method for tabletting without pelletization, saved granulation step, simplifies technique.For the dissolution that further makes the roflumilast sheet meets the requirements, prepare bioavailability high, have definite curative effect, and the satisfactory roflumilast sheet of quality, be necessary the method for direct powder compression is studied.
Summary of the invention
The invention provides a kind of roflumilast sheet and preparation method thereof, the method adopts the method for direct powder compression, has simplified processing step, shortens life cycle of the product, and the roflumilast sheet dissolution for preparing is high, and uniformity of dosage units is qualified.
The invention provides a kind of roflumilast sheet and preparation method thereof, it is characterized in that, comprise following component:
Preparation method is: the roflumilast crude drug is pulverized with jet mill, taken the roflumilast raw material for standby of recipe quantity; The method that adopts equivalent to progressively increase, first the roflumilast raw material is fully mixed with cross-linking sodium carboxymethyl cellulose, the carboxymethyl starch sodium of recipe quantity, fully mix with pregelatinized Starch, microcrystalline Cellulose, vertical compression lactose, the magnesium stearate of recipe quantity successively afterwards; After the material detection level that mixes, conversion answers tabletting heavy according to content, carries out tabletting, regulates the hardness 2～3kg of tablet, and content uniformity ± 5.0% carries out tabletting.
Preferred roflumilast sheet comprises following component:
Preparation method is: the roflumilast crude drug is pulverized with jet mill, taken the roflumilast raw material for standby of recipe quantity; The method that adopts equivalent to progressively increase is first fully mixed the roflumilast raw material with cross-linking sodium carboxymethyl cellulose, the carboxymethyl starch sodium of recipe quantity, fully mixes with recipe quantity pregelatinized Starch, microcrystalline Cellulose, vertical compression lactose, magnesium stearate successively afterwards; After the material detection level that mixes, conversion answers tabletting heavy according to content, carries out tabletting, regulates the hardness 2～3kg of tablet, and content uniformity ± 5.0% carries out tabletting.
Roflumilast raw material poorly water-soluble, the particle diameter of raw material is less, and its specific surface area of the roflumilast of equal in quality is larger, and its area that contacts with dissolution medium is larger, thus the stripping that more is conducive to improve medicine.Study discovery through the inventor, preparation method of the present invention during less than 20um, can reach qualified dissolution rate at the particle diameter of roflumilast 90% particle.As a rule, can cover the equipment such as pulverizer, Universalpulverizer, jet mill raw material is pulverized by hammer crusher, vibromill, turbine grinder, ball mill, thunder, the inventor is through contrasting multiple disintegrating apparatus crushing effect, raw material particle size after discovery employing jet mill is pulverized is all below 20um, can save the step of sieving like this, and improve raw material availability.Thereby the pre-treatment of this product raw material adopts jet mill to carry out micronization processes.
Technique of direct powder compression has higher requirement for compressibility, mouldability and the mobility of mixed-powder, because bulk density and the mobility of each adjuvant is not quite similar, thereby can there be certain difference in the prepared various physical parameters of mixed-powder of adjuvant of variety classes, different proportionings, and these differences can affect tablet compact property and uniformity of dosage units.The adjuvant that direct powder compression is commonly used comprises that microcrystalline Cellulose, lactose, pregelatinized Starch, mannitol are as filler, magnesium stearate, silicon dioxide, Pulvis Talci are as lubricant, also can add as required cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, hyprolose, carboxymethyl starch sodium etc. as disintegrating agent, in the method for the invention, due to crude drug roflumilast indissoluble, therefore added disintegrating agent, to promote the stripping of roflumilast sheet.
Due to roflumilast crude drug process micronization processes of the present invention, below particle diameter 20um, the non-constant of mobility, and roflumilast sheet specification of the present invention is 0.5mg, and proportion is less in prescription, therefore, the kind of adjuvant and the selection of consumption become particularly important, otherwise will affect the tabletting success, or the underproof problem of uniformity of dosage units, the stripping behavior of prepared roflumilast sheet also can be affected in addition.The inventor has done a large amount of research work to the selection of adjuvant.
Because the roflumilast raw material is insoluble in water, add hydrophilic adjuvant will help the stripping of product in the vertical compression prescription.Vertical compression lactose and vertical compression mannitol are water soluble adjuvant, but the experiment discovery adopts these two kinds of water solublity vertical compression adjuvants to carry out powder vertical compression process exploitation, the sticking phenomenon can occur in the tabletting process, and tablet weight variation is larger.For solving the sticking problem, need the amount of magnesium stearate in prescription is improved.When the ratio of magnesium stearate in prescription brought up to 0.8%, we found the not improvement of sticking phenomenon, when this ratio brings up to 1.0%, the sticking phenomenon is resolved, but magnesium stearate is lyophobic dust, when proportion is 1.0% in prescription when it, can obviously reduce the stripping of product.Therefore in prescription, the amount of magnesium stearate should not surpass 1.0% of recipe quantity.
We select the pharmaceutical lactose series of products of German MEGGLE company the vertical compression lactose, attempt the vertical compression lactose of Tablettose80, Tablettose100, three models of FlowLac100 in experimentation, adopted the sample size uniformity, mobility, the compressibility of FlowLac100 preparation all to show well during we find to write out a prescription.In prescription, the RSD value of the sample size uniformity of employing Tablettose80 preparation is bigger than normal; And the prescription of employing Tablettose100, the mobility of its mixed-powder, the performance of compressibility are all not as FlowLac100.
Common microcrystalline Cellulose particle diameter is less, poor fluidity, and be not suitable for the exploitation of vertical compression technique.Microcrystalline Cellulose we select the microcrystalline Cellulose of Japanese Asahi Chemical Industry to study, and finds that in experiment the performance of pH-102 type product is better than pH-301 model and other models, is more suitable for direct powder compression and prepares the roflumilast sheet.
Therefore, in technical scheme of the present invention, the preferred model of vertical compression lactose is FlowLac100, and the preferred model of microcrystalline Cellulose is pH-102.
Through the repeated screening to supplementary product kind and proportioning, obtain four technical schemes of the more excellent embodiment 1-4 of result, each technical scheme comprises that prescription forms and preparation method, the roflumilast sheet good appearance that obtains, technical process is smooth, have good operability, uniformity of dosage units is qualified, and the product dissolution is with former to grind product more consistent.Simultaneously, pleasantly surprised discovery, the stripping behavior of the roflumilast sheet that in above-mentioned four technical schemes, embodiment 4 makes even is better than the former product that grinds.
The invention provides a kind of roflumilast sheet and preparation method thereof, the method adopts the direct powder compression preparation, and production technology is simple, has shortened the production cycle, reduced the cost of equipment and running, the roflumilast sheet good appearance for preparing, technical process is smooth, has good operability, the product dissolution is high, uniformity of dosage units is qualified, can reach good bioavailability at human body, thereby produces good curative effect.
The present invention will be further described below in conjunction with the embodiment of the specific embodiment and Figure of description.
Figure of description
Accompanying drawing 1 embodiment 2, embodiment 4 products and the former stripping comparison diagram that grinds the commercially available prod
The specific embodiment
Embodiment 1
Preparation method: the roflumilast raw material is pulverized with jet mill, taken the roflumilast raw material of 1000 tablet recipe amounts, standby; The method that adopts equivalent to progressively increase is first fully mixed the roflumilast raw material with the cross-linking sodium carboxymethyl cellulose of recipe quantity, fully mixes with microcrystalline Cellulose, vertical compression lactose, the magnesium stearate of recipe quantity successively afterwards; The powder that mixes detects bulk density, and angle of repose, conversion answers tabletting heavy according to content, carries out tabletting, regulates the hardness 2～3kg of tablet, content uniformity ± 5.0%.
Embodiment 2
Preparation method: the roflumilast raw material is pulverized with jet mill, taken the roflumilast raw material of 1000 tablet recipe amounts, standby; The method that adopts equivalent to progressively increase is first fully mixed the roflumilast raw material with the cross-linking sodium carboxymethyl cellulose of recipe quantity, fully mixes with pregelatinized Starch, microcrystalline Cellulose, vertical compression lactose, the magnesium stearate of recipe quantity successively afterwards; After the material detection level that mixes, conversion answers tabletting heavy according to content, carries out tabletting, regulates the hardness 2～3kg of tablet, content uniformity ± 5.0%.
Embodiment 3
Preparation method: the roflumilast raw material is pulverized with jet mill, taken the roflumilast raw material of 1000 tablet recipe amounts, standby; The method that adopts equivalent to progressively increase is first fully mixed the roflumilast raw material with the carboxymethyl starch sodium of recipe quantity, fully mixes with pregelatinized Starch, microcrystalline Cellulose, vertical compression lactose, the magnesium stearate of recipe quantity successively afterwards; After the powder that mixes detected angle of repose, bulk density content, conversion answered tabletting heavy according to content, carries out tabletting, regulates the hardness 2～3kg of tablet, content uniformity ± 5.0%.
Embodiment 4
Preparation method: the roflumilast raw material is pulverized with jet mill, taken the roflumilast raw material of 1000 tablet recipe amounts, standby; The method that adopts equivalent to progressively increase, first the roflumilast raw material is fully mixed with cross-linking sodium carboxymethyl cellulose, the carboxymethyl starch sodium of recipe quantity, fully mix with pregelatinized Starch, microcrystalline Cellulose, vertical compression lactose, the magnesium stearate of recipe quantity successively afterwards; After the material detection level that mixes, conversion answers tabletting heavy according to content, carries out tabletting, regulates the hardness 2～3kg of tablet, content uniformity ± 5.0%.
Above embodiment is measured respectively bulk density, angle of repose, the uniformity of dosage units of mixed powder, and the friability of tablet, the projects such as uniformity of dosage units, tablet weight variation, result is as follows.
The mensuration of embodiment 5 dissolutions
Assay method: get this product, make dissolution medium with 0.3% lauryl sodium sulfate aqueous solution 500ml according to dissolution method, rotating speed is per minute 50 to turn, and gets solution through 30 minutes appropriate, filters, and gets subsequent filtrate as need testing solution; It is appropriate that another precision takes the roflumilast reference substance, after a small amount of dissolve with ethanol, adds 0.4% sodium dodecyl sulfate solution to make the solution that every 1ml approximately contains the 1ug roflumilast, in contrast product solution.As filler, the phosphate with 0.3% is as mobile phase with octadecylsilane chemically bonded silica, and flow velocity is 1ml/min, and the detection wavelength is 216nm.Reference substance solution continuous sample introduction several, the relative standard deviation of its area should be not more than 2.0%, and precision measures need testing solution and reference substance solution 20ul respectively, injects chromatographic column, records chromatogram, by the stripping quantity of external standard method with every of calculated by peak area.Its result is as shown in the table:
Roflumilast sheet dissolution testing result
Above result demonstration, the dissolution of the sample 30min of embodiment 2 and embodiment 4 preparations is more approaching in former triturate.
Choose embodiment 2 and carry out the mensuration of stripping curve with the roflumilast sheet that embodiment 4 prepares in 0.4% lauryl sodium sulfate aqueous solution, respectively at the stripping quantity of 5min, 10min, 15min, 20min, 30min, 45min, 60min sampling test sample, record data are also compared with the stripping curve of listing product, and result is as shown in the table:
Above result shows, embodiment 2 and embodiment 4 are preferred technical scheme, and the In Vitro Dissolution situation of itself and commercially available product has higher similarity, embodiment 4 more preferably wherein, and the stripping behavior is better than the former commercially available prod (seeing accompanying drawing 1) of grinding.
Comparative example 1 (wet granulation method)
Preparation method: the roflumilast raw material is pulverized with jet mill, standby; Take each supplementary material mix homogeneously of recipe quantity, add 4.0% appropriate hyprolose solution soft material processed, wet stock is crossed 30 mesh sieves granulate, wet granular is placed under 60 ℃ of conditions carries out drying, after dry materials, add the magnesium stearate mix homogeneously according to the weight of dried granule, after the material detection level that mixes, conversion answers tabletting heavy according to content, carries out tabletting, regulate the hardness 2～3kg of tablet, content uniformity ± 5.0%.
This product being carried out dissolution in the 500ml0.3% lauryl sodium sulfate aqueous solution detects:
Above result shows, adopts the sample stripping of wet granulation preparation partially slow, and its stripping f2 value is less than 50, can judge that the In Vitro Dissolution behavior of itself and former triturate does not have concordance.
Comparative example 2 (wet granulation method)
Preparation method: the roflumilast raw material is pulverized with jet mill, standby; Take each supplementary material mix homogeneously of recipe quantity, add 5% appropriate PVP K-90 solution soft material processed, wet stock is crossed 30 mesh sieves granulate, wet granular is placed under 60 ℃ of conditions carries out drying, after dry materials, add the magnesium stearate mix homogeneously according to the weight of dried granule, after the material detection level that mixes, conversion answers tabletting heavy according to content, carries out tabletting, regulate the hardness 2～3kg of tablet, content uniformity ± 5.0%.
Stripping curve is measured:
Get this product, make dissolution medium with 0.3% lauryl sodium sulfate aqueous solution 500ml according to dissolution method, rotating speed is per minute 50 to turn, and measures respectively it at the dissolution of 5min, 10min, 15min, 20min, 30min, 45min, 60min.
Above result shows, the sample stripping of adopting above-mentioned wet granulation to prepare is partially slow, and its f2 value is 17, less than 50 the time, can judge that the In Vitro Dissolution behavior of itself and former triturate does not have concordance when the f2 value.After adopting the sample chance water of above formulation and technology preparation, the surface can form sticky floccule, causes roflumilast to be discharged into from tablet in dissolution medium, causes the sample stripping partially slow.
Claims (4)
1. roflumilast sheet and preparation method thereof, is characterized in that, comprises following component:
Preparation method is: the roflumilast crude drug is pulverized with jet mill, taken the roflumilast raw material for standby of recipe quantity; The method that adopts equivalent to progressively increase, first the roflumilast raw material is fully mixed with cross-linking sodium carboxymethyl cellulose, the carboxymethyl starch sodium of recipe quantity, fully mix with pregelatinized Starch, microcrystalline Cellulose, vertical compression lactose, the magnesium stearate of recipe quantity successively afterwards; After the material detection level that mixes, conversion answers tabletting heavy according to content, carries out tabletting, regulates the hardness 2～3kg of tablet, and content uniformity ± 5.0% carries out tabletting.
2. roflumilast sheet according to claim 1 and preparation method thereof, is characterized in that, comprises following component:
Preparation method is: the roflumilast crude drug is pulverized with jet mill, taken the roflumilast raw material for standby of recipe quantity; The method that adopts equivalent to progressively increase, first the roflumilast raw material is fully mixed with cross-linking sodium carboxymethyl cellulose, the carboxymethyl starch sodium of recipe quantity, fully mix with recipe quantity pregelatinized Starch, microcrystalline Cellulose, vertical compression lactose, magnesium stearate successively respectively afterwards; After the material detection level that mixes, conversion answers tabletting heavy according to content, carries out tabletting, regulates the hardness 2～3kg of tablet, and content uniformity ± 5.0% carries out tabletting.
3. roflumilast sheet according to claim 1 and preparation method thereof, is characterized in that described microcrystalline Cellulose model is pH-102.
4. roflumilast sheet according to claim 1 and preparation method thereof, the model that it is characterized in that described vertical compression lactose is FlowLac100.
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| CN201210593342.XA CN103127011B (en) | 2012-12-27 | 2012-12-27 | Roflumilast tablet and preparation method thereof |
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| CN201210593342.XA CN103127011B (en) | 2012-12-27 | 2012-12-27 | Roflumilast tablet and preparation method thereof |
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| CN103127011B CN103127011B (en) | 2014-11-26 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103830195A (en) * | 2014-03-11 | 2014-06-04 | 熊妲妮 | Indacaterol tablet and preparation method thereof |
| CN103976965A (en) * | 2014-05-20 | 2014-08-13 | 朱金强 | Etoncoxib tablet and preparation method thereof |
| CN104027318A (en) * | 2014-06-13 | 2014-09-10 | 青岛市市立医院 | Domperidone tablet and preparation method thereof |
| CN106139161A (en) * | 2016-08-12 | 2016-11-23 | 合肥久诺医药科技有限公司 | A kind of roflumilast clathrate and solid preparation thereof |
| CN111643470A (en) * | 2020-04-30 | 2020-09-11 | 山东希尔康泰药业有限公司 | Preparation process of roflumilast film-coated tablets |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1635909A (en) * | 2002-02-20 | 2005-07-06 | 奥坦纳医药公司 | Oral dosage form containing a PDE 4 inhibitor as an active ingredient and polyvinylpyrrolidon as excipient |
| CN102274222A (en) * | 2011-08-18 | 2011-12-14 | 天津市汉康医药生物技术有限公司 | High-bioavailability roflumilast medicinal composition and preparation method thereof |
| CN102626410A (en) * | 2012-03-16 | 2012-08-08 | 北京万全阳光医学技术有限公司 | Pharmaceutical composition containing roflumilast |
| CN102743353A (en) * | 2012-07-27 | 2012-10-24 | 海南盛科生命科学研究院 | Roflumilast tablet preparation and preparation method thereof |
-
2012
- 2012-12-27 CN CN201210593342.XA patent/CN103127011B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1635909A (en) * | 2002-02-20 | 2005-07-06 | 奥坦纳医药公司 | Oral dosage form containing a PDE 4 inhibitor as an active ingredient and polyvinylpyrrolidon as excipient |
| CN102274222A (en) * | 2011-08-18 | 2011-12-14 | 天津市汉康医药生物技术有限公司 | High-bioavailability roflumilast medicinal composition and preparation method thereof |
| CN102626410A (en) * | 2012-03-16 | 2012-08-08 | 北京万全阳光医学技术有限公司 | Pharmaceutical composition containing roflumilast |
| CN102743353A (en) * | 2012-07-27 | 2012-10-24 | 海南盛科生命科学研究院 | Roflumilast tablet preparation and preparation method thereof |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103830195A (en) * | 2014-03-11 | 2014-06-04 | 熊妲妮 | Indacaterol tablet and preparation method thereof |
| CN103976965A (en) * | 2014-05-20 | 2014-08-13 | 朱金强 | Etoncoxib tablet and preparation method thereof |
| CN104027318A (en) * | 2014-06-13 | 2014-09-10 | 青岛市市立医院 | Domperidone tablet and preparation method thereof |
| CN106139161A (en) * | 2016-08-12 | 2016-11-23 | 合肥久诺医药科技有限公司 | A kind of roflumilast clathrate and solid preparation thereof |
| CN111643470A (en) * | 2020-04-30 | 2020-09-11 | 山东希尔康泰药业有限公司 | Preparation process of roflumilast film-coated tablets |
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| CN103127011B (en) | 2014-11-26 |
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