CN1509711A - Fenfibrate masticatory and its preparation - Google Patents
Fenfibrate masticatory and its preparation Download PDFInfo
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- CN1509711A CN1509711A CNA02128055XA CN02128055A CN1509711A CN 1509711 A CN1509711 A CN 1509711A CN A02128055X A CNA02128055X A CN A02128055XA CN 02128055 A CN02128055 A CN 02128055A CN 1509711 A CN1509711 A CN 1509711A
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- solid dispersion
- fenofibrate
- fenfibrate
- masticatory
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Abstract
A chewing tablet of fenofibrate is prepared from fenofibrate, solid disperser as carrier, filler, disintegrant, flowing aid, lubricant, surfactant and sweetening agent through proportioning, heating the fenofibrate and carrier by water bath, quick cooling for solidifying, drying, breaking, mixing with others, and tabletting.
Description
Technical field:
The present invention is relevant with tablet that is principal agent with the fenofibrate and preparation method thereof.
Background technology:
Fenofibrate belongs to the fibrate fat regulation medicine, existing is that the tablet of principal agent is that the fenofibrate crushing screening is made medicated powder with the fenofibrate, add suitable adjuvant again and be mixed and made into mixture, add flexible material again and make dried granule, dried granule is added mixture-aid agent be mixed and made into granule, the granule tabletting is made the fenofibrate conventional tablet.Use this preparation method, the fenofibrate particle diameter can not make very little, and its drug dissolution can only reach 53.38%, and bioavailability is low, and need obey 300mg every day, divides and takes for three times, takes inconvenience.
Summary of the invention:
The purpose of this invention is to provide a kind of bioavailability height, side effect is little, Fenfibrate masticatory of taking convenience and preparation method thereof.
The present invention is achieved in that
Fenfibrate masticatory of the present invention is a principal agent with the fenofibrate, and its component and consumption are as follows: weight portion:
Fenofibrate 150-250
Solid dispersion carrier 150-250
Filler 100-200
Disintegrating agent 50-130
Fluidizer 1-3
Lubricant 1-3
Surfactant 0-3
Sweeting agent is earlier made solid dispersion with fenofibrate and solid dispersion carrier heating in water bath, rapidly cooling curing, drying, be ground into the solid dispersion powder, make with other component powders mixing, tabletting again.
Solid dispersion carrier of the present invention is a kind of among polyethylene glycol 6000 and the PVP or two kinds, fenofibrate: solid dispersion carrier=1: (0.5-1.5), and weight ratio.
Fenofibrate of the present invention: solid dispersion carrier=1: 1, weight ratio.
Solid dispersion carrier of the present invention is a polyethylene glycol 6000, filler is a lactose, disintegrating agent is two kinds of crospolyvinylpyrrolidone and carboxymethyl starch sodium, its consumption is respectively 30-70 and 20-60 (weight portion), fluidizer is micropowder silica gel, lubricant is hard magnesium acetate, and surfactant is a sodium lauryl sulphate, and sweeting agent is an aspartame.
The present invention adds the surfactant sodium lauryl sulphate of fenofibrate content 1% when the preparation solid dispersion.
Its component of the present invention and consumption are as follows:
Fenofibrate 200
Polyethylene glycol 6000 200
Lactose 150
XLPE ketopyrrolidine 50
Carboxymethyl starch sodium 40
Micropowder silica gel 2
Magnesium stearate 2
Sodium lauryl sulphate 2
Aspartame 10
The preparation method and the step thereof of Fenfibrate masticatory of the present invention are as follows:
1. take by weighing fenofibrate crude drug and polyethylene glycol 6000 respectively and place beaker, in 70-95 ℃ of heating in water bath 1-2 hour, stir and made its fusion be hyaloid in 30-50 minute, add sodium lauryl sulphate 1-3 weight portion, stir evenly, in pre-cooled vessel, make its rapidly 0-6 ℃ of cooling and solidifying in 3-15 minute, at room temperature dry, pulverize, cross the 60-100 mesh sieve, it is standby to make the solid dispersion powder
2. take by weighing solid dispersion powder 300-500 weight portion respectively, mix successively, cross the 40-80 mesh sieve for several times with the powder of other component in the prescription, mixing,
3. survey content, tabletting, packing.
Water bath heating temperature is 85 ℃ in manufacture method of the present invention and the step thereof (1), time is 1.5 hours, stirred 40 minutes, fusion is hyaloid mixing material to be inclined to and is chilled to 4 ℃ stainless steel disc in advance, make it in 10 minutes, be cooled to 4 ℃ rapidly, pulverize the back and cross 80 mesh sieves, the mixed-powder in the step (2) is crossed 60 mesh sieves 3 times.
The prescription foundation of chewable tablet of the present invention
1, principal agent physicochemical property
The FENOBRATE thing is white or off-white color crystalline powder, odorless, tasteless, and fusing point is for being 78～82 ℃; This product is very easily dissolving in chloroform, and is easily molten in acetone or ether, molten in the ethanol part omitted, almost insoluble in water.
2, solid dispersion research
(1) selection of solid dispersion carrier
According to principal agent character, the present invention has selected compatible with it two kinds of water-solubility carrier PEG6000 and PVP, is carrier with list with PEG6000, single is carrier with PVP, share PEG6000 and PVP (1: 0.1) and compare screening for three kinds of modes of joint vector prepare solid dispersion respectively, and its external dissolution characteristic studied, the results are shown in Table 1.
Table 1 different carriers prepares the experiment of solid dispersion and compares
Experiment is PEG6000 PVPK-30 PEG6000+PVPK-30 relatively
Principal agent-carrier was than (w/w) 1: 11: 11: (1+0.1)
Preparation method fusion method solvent method solvent-dissolve method
Dispersion properties is more loose, easily pulverizes toughness, is difficult for pulverizing easily pulverizing
Economic consideration does not need solvent, the low organic solvent that needs of cost, and cost is high need a small amount of organic solvent
Dissolution (45 minutes) 91.4% 77.8% 90.4%
As shown in Table 1, with single be that the solid dispersion dissolution of preparing carriers is higher relatively with PEG, be easy to pulverize, and preparation method is simple, cost is low, so preferred PEG6000 is the carrier for preparing fenofibrate solid dispersion.
(2) medicine-carrier ratio determines
For further preferably best pharmaceutical carrier ratio, we have designed fenofibrate and PEG6000 prepares solid dispersion with 1: 0.5,1: 1,1: 1.5 three kinds of ratios respectively, with the dissolution are to investigate index to screen, and the results are shown in Table 2.
The selection of table 2 medicine-carrier ratio
Medicine-carrier was than (w/w) 1: 0.5 1: 11: 1.5
Dissolution (%) 25 minutes 76.17 89.34 91.25
45 minutes 87.18 91.49 92.21
As shown in Table 2, when medicine--when the carrier ratio is 1: 1 and 1: 1.5, prepared solid dispersion dissolution was apparently higher than 1: 0.5, and the above two out-degree difference are not obvious, so consider from preparation angle and economic angle, our preferred agents--the carrier ratio is 1: 1 preparation fenofibrate solid dispersion.
(3) diameter of aspirin particle is observed
Get fenofibrate solid dispersion powder (crossing 80 mesh sieves) and put the microscopically observation, its diameter of aspirin particle reaches the requirement of micronize preparation to particle diameter less than 10 μ m.
(4) surfactant selects for use
We add the surfactant sodium lauryl sulphate of drug content 1% to improve the wettability of fenofibrate solid dispersion when the preparation solid dispersion.
The research of chewable tablet prescription
(1) prescription screening
According to principal agent character and construction features, we have selected multiple compatible with it adjuvant, have designed the comparison that experimentizes of five kinds of prescriptions by the characteristics of chewable tablet, the results are shown in Table 3.
Test 12345
Relatively
Solid dispersion 402 solid dispersion 402 solid dispersion 402 solid dispersion 402 solid dispersion 402
Cross-linked pvp 180 lactose 180 lactose 180 lactose 180 lactose 180
Aspartame 15 aspartames 8 carboxymethyl starch sodium 40 cross-linked pvps 40 PVP 50
Prescription micropowder silica gel 2 micropowder silica gels 2 aspartames 10 aspartames 10 carboxymethyl starch sodium 40
(mg/ sheet) magnesium stearate 2 stearic acid pincers 2 micropowder silica gels 2 micropowder silica gels 2 aspartames 10
2 micropowder silica gels 2 of stearic acid pincers 2 magnesium stearate
Magnesium stearate 2
Technology profile principal agent and auxiliary materials and mixing, direct powder compression
Tablet mouthfeel difference is good
Disintegration (min) 3～4 30～34 20～2 3 17～20 10～15
Body of powder end angle α (°) 46.8 43.1 39.2 41.3 36.6
As shown in Table 3, No. 5 the prescription powder flowbility is better, is easy to tabletting, and the tablet mouthfeel of making is better, and disintegrate is better relatively, meets the requirement of chewable tablet, so preferred No. 5 prescriptions are the prescription of preparation Fenfibrate masticatory.
(2) Study on Preparation
Prerun contains more PEG6000 in the Fenfibrate masticatory prescription as can be known by experiment, and viscosity is big, the difficulty of granulating, again this product heating back easily deliquescing be clamminess, should not dry, so be not suitable for wet granulation.On the basis of trial test, we select for use, and tabletting and two kinds of technologies of direct powder compression compare behind the dry granulation.Through experiment relatively, the chewable tablet of two kinds of method preparations, its outward appearance, mouthfeel all do not have significant difference, weight differential (the assay method reference " 2000 editions two attached IA of Chinese pharmacopoeia) all meet the requirements.Because the technology of tabletting is comparatively loaded down with trivial details behind the dry granulation, and the prescription that we select for use (seeing Table No. 5 prescriptions in 3) powder flowbility is good, and compressibility is good, is suitable for direct powder compression, still the prepared Fenfibrate masticatory of choice of powder direct compression.
(3) demonstration test
On the basis of prescription screening and Study on Preparation; we select No. 5 prescriptions (seeing Table 3) direct powder compression for use; with the dissolution is to investigate index; comparison experimentizes with import fenofibrate micronize capsule (French Li Bofuni drugmaker) and homemade ordinary tablet (Xuzhou pharmaceutical factory); the result shows; the dissolution of Fenfibrate masticatory reaches the capsular requirement of import micronize; more homemade ordinary tablet improves a lot, and (dissolution is respectively in 45 minutes: chewable tablet 85.82% of the present invention; import micronize capsule 84.05%, homemade ordinary tablet 53.38%).
The principal agent particle diameter is little in the Fenfibrate masticatory of the present invention, reach about 10 μ m, and the dissolution height, 45 minutes dissolution exceeds 1/3 of ordinary tablet.The bioavailability height is more than 130% of ordinary tablet, and only need obey 200mg every day, and a twice-daily gets final product, and patient shows very big compliance, and side effect reduces.Water not when taking medicine is taken more convenient.
The preparation method of Fenfibrate masticatory of the present invention is to utilize water-solubility carrier to prepare solid dispersion, the high degree of dispersion state that not only can keep medicine, and medicine had good wettability, and can increase the dissolution rate and the dissolubility of medicine, improve bioavailability of medicament.
The specific embodiment:
1, takes by weighing each 200g of fenofibrate crude drug and PEG6000 respectively and put mixing in the beaker,, stir in 85 ℃ of heating in water bath, make fusion be hyaloid, add sodium lauryl sulphate 2g, stir, incline in the stainless steel disc of pre-cooling, make it in 10 minutes, be cooled to 4 ℃ of curing rapidly, drying at room temperature is pulverized, and crosses 80 mesh sieves, make the solid dispersion powder, standby.
2, take by weighing solid dispersion powder 402g, lactose 150g, crospolyvinylpyrrolidone 50g, carboxymethyl starch sodium 40g, aspartame 10g respectively, micropowder silica gel 2g, magnesium stearate 2g mix successively, cross 60 mesh sieves 3 times, mixing.
3, survey content, tabletting, packing.
The effect of each adjuvant in prescription
Polyethylene glycol 6000 solid dispersion carrier
The sodium lauryl sulphate surfactant
The lactose filler
The crospolyvinylpyrrolidone disintegrating agent
The carboxymethyl starch sodium disintegrating agent
The aspartame sweeting agent
The micropowder silica gel fluidizer
Magnesium
Former, adjuvant is originated and quality standard
| The title source |
| Vertical letter medication chemistry Co., Ltd's Chinese Pharmacopoeia version PEG6000 in 2000 PVG Gao Nan chemical plant Chinese Pharmacopoeia version lactose in 2000 Shanghai, fenofibrate Jinhua Hua Mao dairy products are sold what agent metric system pharmaceutical factory Chinese Pharmacopoeia version superfine silica gel powder in 2000 Guangzhou Guangdong, people chemical plant Q/WS-1-82 dolomol YingKou AODA Pharmaceutical CO.,LTD Chinese Pharmacopoeia version in 2000 of Guangzhou, food chemistry factory Chinese Pharmacopoeia version aspartame ore deposit in 2000, Co., Ltd's Chinese Pharmacopoeia international special product (ISP) company's American Pharmacopeia 23 editions sodium carboxymethyl starch Huzhou Cities water chestnut lake of version PVPP in 2000 |
Claims (8)
1, Fenfibrate masticatory is a principal agent with the fenofibrate, it is characterized in that its component and consumption are as follows: weight portion:
Fenofibrate 150-250
Solid dispersion carrier 150-250
Filler 100-200
Disintegrating agent 50-130
Fluidizer 1-3
Lubricant 1-3
Surfactant 0-3
Sweeting agent is earlier made solid dispersion with fenofibrate and solid dispersion carrier heating in water bath, rapidly cooling curing, drying, be ground into the solid dispersion powder, make with other component powders mixing, tabletting again.
2, Fenfibrate masticatory according to claim 1 is characterized in that said solid dispersion carrier is a kind of among polyethylene glycol 6000 and the PVP or two kinds, fenofibrate: solid dispersion carrier=1: (0.5-1.5), and weight ratio.
3, Fenfibrate masticatory according to claim 1 is characterized in that fenofibrate: solid dispersion carrier=1: 1, weight ratio.
4, Fenfibrate masticatory according to claim 1, it is characterized in that said solid dispersion carrier is a polyethylene glycol 6000, filler is a lactose, disintegrating agent is two kinds of crospolyvinylpyrrolidone and carboxymethyl starch sodium, its consumption is respectively 30-70 and 20-60 (weight portion), and fluidizer is micropowder silica gel, and lubricant is hard magnesium acetate, surfactant is a sodium lauryl sulphate, and sweeting agent is an aspartame.
5, Fenfibrate masticatory according to claim 1 is characterized in that adding the surfactant sodium lauryl sulphate of fenofibrate content 1% when the preparation solid dispersion.
6, Fenfibrate masticatory according to claim 1 is characterized in that its component and consumption are as follows:
Fenofibrate 200
Polyethylene glycol 6000 200
Lactose 150
XLPE ketopyrrolidine 50
Carboxymethyl starch sodium 40
Micropowder silica gel 2
Magnesium stearate 2
Sodium lauryl sulphate 2
Aspartame 10
7,, it is characterized in that step is as follows according to the preparation method of the described Fenfibrate masticatory of claim 1-7:
1. take by weighing fenofibrate crude drug and polyethylene glycol 6000 respectively and place beaker, in 70-95 ℃ of heating in water bath 1-2 hour, stir and made its fusion be hyaloid in 30-50 minute, add sodium lauryl sulphate 1-3 weight portion, stir evenly, in pre-cooled vessel, make it in 3-15 minute, be cooled to 0-6 ℃ and solidify rapidly, at room temperature dry, pulverize, cross the 60-100 mesh sieve, it is standby to make the solid dispersion powder
2. take by weighing solid dispersion powder 300-500 weight portion respectively, mix successively, cross the 40-80 mesh sieve for several times with the powder of other component in the prescription, mixing,
3. survey content, tabletting, packing.
8, Fenfibrate masticatory manufacture method according to claim 1, it is characterized in that water bath heating temperature is 85 ℃ in the step (1), time is 1.5 hours, stirred 40 minutes, fusion is hyaloid mixing material to be inclined to and is chilled to 4 ℃ stainless steel disc in advance, make it be cooled to 4 ℃ rapidly in 10 minutes, pulverize the back and cross 80 mesh sieves, the mixed-powder in the step (2) is crossed 60 mesh sieves 3 times.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA02128055XA CN1509711A (en) | 2002-12-20 | 2002-12-20 | Fenfibrate masticatory and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA02128055XA CN1509711A (en) | 2002-12-20 | 2002-12-20 | Fenfibrate masticatory and its preparation |
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| Publication Number | Publication Date |
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| CN1509711A true CN1509711A (en) | 2004-07-07 |
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| CNA02128055XA Pending CN1509711A (en) | 2002-12-20 | 2002-12-20 | Fenfibrate masticatory and its preparation |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102458373A (en) * | 2009-05-27 | 2012-05-16 | 株式会社三养生物制药 | Microspheres with improved bioavailability containing poorly water-soluble drugs, and method for preparing same |
| CN104784135A (en) * | 2015-04-20 | 2015-07-22 | 鲁南贝特制药有限公司 | Finasteride tablets |
| CN104784132A (en) * | 2014-01-17 | 2015-07-22 | 南京瑞尔医药有限公司 | Clarithromycin dispersible tablet composition |
| CN106727338A (en) * | 2016-12-22 | 2017-05-31 | 广州中大南沙科技创新产业园有限公司 | Fenofibrate solid dispersion and its preparation method and application |
| CN110354087A (en) * | 2019-08-23 | 2019-10-22 | 东莞市金美济药业有限公司 | A kind of fenofibrate dispersible tablet and preparation method thereof |
-
2002
- 2002-12-20 CN CNA02128055XA patent/CN1509711A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102458373A (en) * | 2009-05-27 | 2012-05-16 | 株式会社三养生物制药 | Microspheres with improved bioavailability containing poorly water-soluble drugs, and method for preparing same |
| US9511026B2 (en) | 2009-05-27 | 2016-12-06 | Samyang Biopharmaceuticals Corporation | Poorly soluble drug containing microspheres with improved bioavailability and method of preparing the same |
| CN104784132A (en) * | 2014-01-17 | 2015-07-22 | 南京瑞尔医药有限公司 | Clarithromycin dispersible tablet composition |
| CN104784132B (en) * | 2014-01-17 | 2019-04-09 | 南京海鲸药业有限公司 | A kind of clarithromycin composition |
| CN104784135A (en) * | 2015-04-20 | 2015-07-22 | 鲁南贝特制药有限公司 | Finasteride tablets |
| CN104784135B (en) * | 2015-04-20 | 2018-05-11 | 鲁南贝特制药有限公司 | A kind of Finasteride tablet |
| CN106727338A (en) * | 2016-12-22 | 2017-05-31 | 广州中大南沙科技创新产业园有限公司 | Fenofibrate solid dispersion and its preparation method and application |
| CN106727338B (en) * | 2016-12-22 | 2020-01-14 | 广州中大南沙科技创新产业园有限公司 | Fenofibrate solid dispersion and preparation method and application thereof |
| CN110354087A (en) * | 2019-08-23 | 2019-10-22 | 东莞市金美济药业有限公司 | A kind of fenofibrate dispersible tablet and preparation method thereof |
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