CN101642433A - Nimesulide liposome solid preparation and preparation method of drug composite thereof - Google Patents
Nimesulide liposome solid preparation and preparation method of drug composite thereof Download PDFInfo
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Abstract
The invention provides a Nimesulide liposome solid preparation and a preparation method of the drug composite thereof. For the Nimesulide liposome solid preparation of the invention, the active ingredient Nimesulide is prepared into liposome and then prepared into Nimesulide solid preparation with other ingredients, wherein the liposome is prepared by the following ingredients according to parts by weight: 1 part of Nimesulide, 3-10 parts of lauric acid glycerol monolaurate, 0.5-4 parts of cholesterol, and 0.1-2 parts of poloxamer188. Compared with the existing Nimesulide liposome solid preparation, the Nimesulide of the invention has high dissolution rate and improved bioavailability, and overcomes the detect that the bioavailability of the Nimesulide liposome solid preparation in the prior art is low.
Description
Technical field
The present invention relates to a kind of nimesulide liposome solid preparation, specifically, the solid preparation that the invention provides a kind of Nimesulide liposome and pharmaceutical composition thereof with and preparation method thereof, belong to medical technical field.
Background technology
Nimesulide (Nimesulide), chemical name is: 4-nitro-2-phenoxy group sulfonyl methane aniline, molecular formula: C
13H
12N
2O
5S, molecular weight: 308.3, chemical structural formula:
This product belongs to nonsteroidal antiinflammatory drug, has antiinflammatory, analgesia, refrigeration function.Its mechanism of action is unclear fully as yet, may mainly discharge relevant with the oxidation reaction of polymorphonuclear leukocyte with synthetic, the leukocytic medium that suppresses prostaglandin.According to reports, nimesulide is by oral absorption, and the back of taking medicine reached maximum plasma concentration in 1～2 hour, and the half-life is 3～5 hours, and 6～8 hours still can continuous action.This product accumulation phenomenon can not occur almost all by urine excretion even repeatedly take yet.Can be used for chronic arthritis disease (as rheumatoid arthritis and osteoarthritis etc.) clinically, pain and inflammation behind operation and the acute injury, the pain that the ear nasopharynx inflam mation causes, the treatment of the symptoms such as heating that dysmenorrhea, upper respiratory tract infection cause.
Disclose a kind of controlled release composition that contains nimesulide among the Chinese patent CN1399543A, formed as active medicine, the pharmaceutical excipient that accounts for one or more controlled-release materials of compositions 0.1%-99%w/w and account for compositions 0%-90%w/w by accounting for nimesulide that compositions is no more than 99%w/w.Disclose a kind of preparation method of Nimesulide sustained-release dropping pill among the Chinese patent CN101269034A, formed by 10-40% nimesulide and 40-80% hydrophilic framework material and 10-30% hydrophobicity framework material.Disclose a kind of Nimesulide sustained release medicinal composition among the Chinese patent CN1723883A, formed by nimesulide and hypromellose, ethyl cellulose, lactose and magnesium stearate.Above-mentioned Nimesulide sustained-release, controlled release pharmaceutical compositions discharge slower, and its half-life is can not discharge utilization fully in 3-5 hour, greatly reduces bioavailability, has influenced drug effect.
Chinese patent CN1199335A discloses a kind of local application's preparation that contains nimesulide, form by 0.1-15% nimesulide, 0.1-10% phospholipid and 0.1-10% acid, it can be gel, cream, unguentum, lotion, foam etc., be the external partial medication, drug effect is slow, availability is low, just plays local temporary anti-inflammatory analgesic action, can't compare with injecting drug use with oral medication.
Nimesulide is insoluble in water, its half-life is short, be suitable for preparing common oral administered dosage form or injection type, the inventor is through long-term conscientious research, beyond thought discovery is applied to contain a kind of novel form liposome of targeting drug delivery system in the pharmaceutical composition of nimesulide, solved the poorly soluble problem of nimesulide, improved the drug effect and the bioavailability of nimesulide liposome solid preparation, thereby finished the present invention.
Liposome (liposomes) is dispersed in phospholipid by Britain scholar Bangham and Standish at first and finds when carrying out electron microscopic observation in the water.Phospholipid is dispersed in and forms multilamelar vesicles, every layer of bilayer that is lipid in the water naturally; Separated by water between vesicle central authorities and each layer, the about 4nm of bilayer thickness, the bimolecular folliculus with this similar biofilm structure became liposome afterwards.
Liposome research is that liposome is meant that the earliest the natural grease compounds is suspended in the vesicle with double seal structure that forms in the water, now also can be prepared by the phosphatide cpd of synthetic when previous very active field.People such as late 1960s Rahman at first use liposome as pharmaceutical carrier, in recent years, continuous progress along with biotechnology, liposome preparation technology is progressively perfect, the liposome mechanism of action is further illustrated, liposome is fit to vivo degradation, avirulence and non-immunogenicity in addition, and particularly great number tested data proof liposome can improve the Drug therapy index, reduces drug toxicity and reduce drug side effect as pharmaceutical carrier, and reduces advantage such as drug dose.
Summary of the invention
There is the defective that the active component dissolution is poor, bioavailability is low at nimesulide liposome solid preparation in the prior art, the object of the present invention is to provide a kind of nimesulide liposome solid preparation of improving bioavailability, specifically, a kind of Nimesulide liposome and solid composite medicament thereof are provided, by wrapping up with liposome, solve the defective that nimesulide liposome solid preparation exists, improved the drug effect and the bioavailability of preparation.
The technical scheme that the present invention solves is as follows:
The invention provides a kind of nimesulide liposome solid preparation, it is made up of nimesulide and acceptable accessories, it is characterized in that making nimesulide liposome solid preparation with other adjuvants again after nimesulide is made liposome.
Above-mentioned described nimesulide liposome solid preparation, wherein said liposome is made by following parts by weight of component: 1 part of nimesulide, 3～10 parts of glycerol monolaurate, 0.5～4 part in cholesterol, 188 0.1～2 parts of poloxamers.
Further, the above-mentioned described nimesulide liposome solid preparation of the present invention, wherein said liposome, component can also comprise the pharmaceutically acceptable buffer salt solution of regulating pH value to 5.5～6.5.Described buffer salt solution for example is selected from phosphate buffer, citrate buffer, carbonate buffer solution, borate buffer solution, the acetate buffer one or more.
Above-mentioned described nimesulide liposome solid preparation, wherein said liposome is to make by the method that comprises the steps: (1) is dissolved in nimesulide, glycerol monolaurate, cholesterol and poloxamer 188 in the organic solvent, mix homogeneously makes immobilized artificial membrane after organic solvent is removed in decompression; (2) add buffer salt solution and make the complete aquation of immobilized artificial membrane, even matter emulsifying makes liposome turbid liquor; (3) with liposome turbid liquor lyophilization or spray drying, make Nimesulide liposome.
Above-mentioned described nimesulide liposome solid preparation, wherein said organic solvent for example can be selected from ethanol, chloroform, methanol, the tert-butyl alcohol, n-butyl alcohol, isopropyl alcohol, acetone, ether, benzyl alcohol, the normal hexane one or more.
Preferably, the above-mentioned described nimesulide liposome solid preparation of the present invention is characterized in that being made by following components in weight percentage: Nimesulide liposome 5%-40%, diluent 10%-60%, disintegrating agent 1%-5%, binding agent 0.5%-5%, correctives 0%-20%, lubricant 0%-5%.
Above-mentioned described nimesulide liposome solid preparation, wherein said adjuvant, for example diluent, disintegrating agent, binding agent, correctives, lubricant are not particularly limited, and can be the adjuvant that pharmaceutically is suitable for.For example:
Described diluent is selected from one or more in microcrystalline Cellulose, starch, pregelatinized Starch, lactose, sorbitol, mannitol, dextrin, calcium sulfate, the calcium hydrogen phosphate; Perhaps
Described disintegrating agent is selected from one or more in carboxymethylstach sodium, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, the dried starch; Perhaps
Described binding agent is selected from one or more in 30 POVIDONE K 30 BP/USP 30, hypromellose, starch slurry, sodium carboxymethyl cellulose, the syrup; Perhaps
Described correctives is selected from one or more in sucrose, Aspartane, saccharin sodium, the steviosin; Perhaps
Described lubricant is selected from one or more in magnesium stearate, Pulvis Talci, colloidality silicon dioxide, PEG6000, the sodium lauryl sulphate etc.
Preferably, the above-mentioned described nimesulide liposome solid preparation of the present invention is characterized in that described solid preparation is granule, tablet, capsule, dispersible tablet or dry suspension.
As another goal of the invention of the present invention, provide the above-mentioned described nimesulide of a kind of preparation solid method, it comprises the steps:
(1) Nimesulide liposome is pulverized, crossed 80 mesh sieves, standby;
(2) get diluent, disintegrating agent and correctives, cross 80 mesh sieves, mix, standby;
(3) with above-mentioned supplementary material mix homogeneously, add binder solution system soft material, the granulation of sieving, oven dry, the adding mix lubricant is even, and granulate gets the nimesulide granule;
(4) granule is carried out packing or tabletting, make nimesulide liposome solid preparation.
Nimesulide liposome solid pharmaceutical composition provided by the invention compared with prior art, has beyond thought effect, and major advantage is as follows:
(1) nimesulide is wrapped in the liposome, has solved poorly soluble problem, has improved the drug effect and the bioavailability of preparation, has guaranteed product quality;
(2) pharmaceutical carrier liposome vivo degradation, avirulence and non-immunogenicity, and can improve the Drug therapy index, reduce drug toxicity and reduce drug side effect;
(3) adopt conventional process equipment, but commercial scale, high efficiency production, and constant product quality is a kind of uniqueness and blanket, the low-cost industrial preparation method.
Nimesulide liposome pharmaceutical composition provided by the invention carries out stability test and investigates, and places 10 days under 60 ℃ of high temperature, illumination 4500Lx condition, and every detection index has no significant change; Accelerated test is 6 months under 40 ℃ of high temperature, relative humidity 75% ± 5% condition, and every detection index does not have significant change; Long term test is 18 months under 25 ℃ of high temperature, relative humidity 60% ± 10% condition, and every detection index does not have significant change.
Nimesulide liposome pharmaceutical composition provided by the invention carries out acute toxicity test, abnormal toxicity test and heat source check, and is all up to specification, and safety obtains proof.
The specific embodiment
Further specify the present invention by the following examples, but should not be construed as limitation of the present invention.
The preparation of embodiment 1 Nimesulide liposome
Prescription: nimesulide 50g
Glycerol monolaurate 150g
Cholesterol 25g
Poloxamer 188 100g
Preparation technology
(1) 50g nimesulide, 150g glycerol monolaurate, 25g cholesterol and 100g poloxamer 188 are dissolved in the 800ml dehydrated alcohol, mix homogeneously, dehydrated alcohol is removed in decompression on rotary film evaporator, makes immobilized artificial membrane;
(2) add pH=5.5 phosphoric acid-sodium hydrogen phosphate buffer 800ml, jolting is stirred and is made the complete aquation of immobilized artificial membrane, and at a high speed even matter emulsifying makes liposome turbid liquor;
(3) with the suspension lyophilization, make Nimesulide liposome.
The preparation of Comparative Examples 1 Nimesulide liposome
Prescription: nimesulide 50g
Glycerol monolaurate 140g
Cholesterol 22g
Poloxamer 188 120g
Preparation technology
(1) 50g nimesulide, 140g glycerol monolaurate, 22g cholesterol and 120g poloxamer 188 are dissolved in the 800ml dehydrated alcohol, mix homogeneously, dehydrated alcohol is removed in decompression on rotary film evaporator, makes immobilized artificial membrane;
(2) add pH=5.5 phosphoric acid-sodium hydrogen phosphate buffer 800ml, jolting is stirred and is made the complete aquation of immobilized artificial membrane, and at a high speed even matter emulsifying makes liposome turbid liquor;
(3) with the suspension lyophilization, make Nimesulide liposome.
The preparation of embodiment 2 Nimesulide liposomes
Prescription: nimesulide 100g
Glycerol monolaurate 1000g
Cholesterol 100g
Poloxamer 188 10g
Preparation technology
(1) 100g nimesulide, 1000g glycerol monolaurate, 100g cholesterol and 10g poloxamer 188 are dissolved in the 2000ml dehydrated alcohol, mix homogeneously, dehydrated alcohol is removed in decompression on rotary film evaporator, makes immobilized artificial membrane;
(2) add pH=6.0 acetic acid-sodium-acetate buffer 1000ml, jolting is stirred and is made the complete aquation of immobilized artificial membrane, and at a high speed even matter emulsifying makes liposome turbid liquor;
(3) with the suspension spray drying, make Nimesulide liposome.
The preparation of Comparative Examples 2 Nimesulide liposomes
Prescription: nimesulide 100g
Glycerol monolaurate 1100g
Cholesterol 420g
Poloxamer 188 8g
Preparation technology
(1) 100g nimesulide, 1100g glycerol monolaurate, 420g cholesterol and 8g poloxamer 188 are dissolved in the 2000ml dehydrated alcohol, mix homogeneously, dehydrated alcohol is removed in decompression on rotary film evaporator, makes immobilized artificial membrane;
(2) add pH=6.0 acetic acid-sodium-acetate buffer 1000ml, jolting is stirred and is made the complete aquation of immobilized artificial membrane, and at a high speed even matter emulsifying makes liposome turbid liquor;
(3) with the suspension spray drying, make Nimesulide liposome.
The preparation of embodiment 3 Nimesulide liposomes
Prescription: nimesulide 75g
Glycerol monolaurate 400g
Cholesterol 300g
Poloxamer 188 150g
Preparation technology
(1) 75g nimesulide, 400g glycerol monolaurate, 300g cholesterol and 150g poloxamer 188 are dissolved in the 2000ml dehydrated alcohol, mix homogeneously, dehydrated alcohol is removed in decompression on rotary film evaporator, makes immobilized artificial membrane;
(2) add pH=6.5 citric acid-sodium citrate buffer 2000ml, jolting is stirred and is made the complete aquation of immobilized artificial membrane, and at a high speed even matter emulsifying makes liposome turbid liquor;
(3) with the suspension lyophilization, make Nimesulide liposome.
The particulate preparation of embodiment 4 nimesulides
The Nimesulide liposome of embodiment 1 (in nimesulide) 50g
Lactose 300g
Starch 75g
Low-substituted hydroxypropyl cellulose 10g
30 POVIDONE K 30 BP/USP 30 5g
Sucrose 250g
Aspartane 20g
Preparation technology
(1) liposome that will contain the 50g nimesulide is pulverized, and crosses 80 mesh sieves, and is standby;
(2) take by weighing 300g lactose, 75g starch, 10g low-substituted hydroxypropyl cellulose, 250g sucrose and 20g Aspartane, cross 80 mesh sieves, mix, standby;
(3) with above-mentioned supplementary material mix homogeneously, add 5% 30 POVIDONE K 30 BP/USP
3060% alcoholic solution system soft material is crossed 20 mesh sieves and is granulated, 60 ℃ of oven dry, and 18 mesh sieve granulate get the nimesulide granule.
(4) with above-mentioned dried granules packing, make the nimesulide granule.
The preparation of embodiment 5 nimesulide dispersible tablets
The Nimesulide liposome of embodiment 2 (in nimesulide) 75g
Microcrystalline Cellulose 70g
Carboxymethylstach sodium 8g
Polyvinylpolypyrrolidone 10g
Hypromellose 3g
Saccharin sodium 10g
Magnesium stearate 2g
Preparation technology
(1) liposome that will contain the 75g nimesulide is pulverized, and crosses 80 mesh sieves, and is standby;
(2) take by weighing 70g microcrystalline Cellulose, 8g carboxymethylstach sodium, 10g polyvinylpolypyrrolidone, 10g saccharin sodium, cross 80 mesh sieves, mix, standby;
(3) with above-mentioned supplementary material mix homogeneously, add 2% hypromellose, 50% alcoholic solution system soft material, to cross 20 mesh sieves and granulate, 55 ℃ of oven dry add 2g magnesium stearate mix homogeneously, and 18 mesh sieve granulate get the nimesulide granule.
(4), make the nimesulide dispersible tablet with the dried granules tabletting.
The particulate preparation of embodiment 6 nimesulides
The Nimesulide liposome of embodiment 3 (in nimesulide) 100g
Pregelatinized Starch 120g
Dextrin 550g
Dried starch 50g
Syrup 200g
Sucrose 700g
Steviosin 75g
Preparation technology
(1) liposome that will contain the 100g nimesulide is pulverized, and crosses 80 mesh sieves, and is standby;
(2) take by weighing 120g pregelatinized Starch, 550g dextrin, 50g dried starch, 700g sucrose and 75g steviosin, cross 80 mesh sieves, mix, standby;
(3) with above-mentioned supplementary material mix homogeneously, add syrup 200g system soft material, cross 20 mesh sieves and granulate, 50 ℃ of oven dry, 18 mesh sieve granulate get the nimesulide granule.
The preparation of embodiment 7 nimesulide sheets
The Nimesulide liposome of embodiment 1 (in nimesulide) 50g
Microcrystalline Cellulose 30g
Lactose 50g
Carboxymethylstach sodium 6g
30 POVIDONE K 30 BP/USP 30 5g
Magnesium stearate 1.3g
Preparation technology
(1) liposome that will contain the 50g nimesulide is pulverized, and crosses 80 mesh sieves, and is standby;
(2) take by weighing 30g microcrystalline Cellulose, 50g lactose, 6g carboxymethylstach sodium, cross 80 mesh sieves, mix, standby;
(3) with above-mentioned supplementary material mix homogeneously, add 5% 30 POVIDONE K 30 BP/USP
3060% alcoholic solution system soft material is crossed 20 mesh sieves and is granulated, and 60 ℃ of oven dry add 1.3g magnesium stearate mix homogeneously, and 18 mesh sieve granulate get the nimesulide granule.
(4), make the nimesulide sheet with the dried granules tabletting.
The capsular preparation of embodiment 8 nimesulides
The Nimesulide liposome of embodiment 2 (in nimesulide) 50g
Dried starch 15g
Microcrystalline Cellulose 80g
30 POVIDONE K 30 BP/USP 30 4g
Magnesium stearate 1.0g
Pulvis Talci 2.0g
Preparation technology
(1) liposome that will contain the 50g nimesulide is pulverized, and crosses 80 mesh sieves, and is standby;
(2) take by weighing 80g microcrystalline Cellulose, 15g dried starch, cross 80 mesh sieves, mix, standby;
(3) with above-mentioned supplementary material mix homogeneously, add 3% 30 POVIDONE K 30 BP/USP
3080% alcoholic solution system soft material is crossed 24 mesh sieves and is granulated, and 55 ℃ of oven dry add 1.0g magnesium stearate and 2.0g Pulvis Talci mix homogeneously, and 20 mesh sieve granulate get the nimesulide granule.
(4), make the nimesulide capsule with the dried granules packing.
The mensuration of test example 1 envelop rate
Get the Liposomal formulation of embodiment 1-2 and Comparative Examples 1-2 preparation, the total content that high performance liquid chromatography detects nimesulide is M, selects for use column chromatography to separate liposome.
Get 1.5g sephadex G-50, soak more than the swelling 12h with the pH6.8 phosphate buffer, pack in the chromatographic column (200 * 10mm) into, with above-mentioned phosphate buffer flushing balance, getting the Nimesulide liposome that embodiment 1-2 and Comparative Examples 1-2 obtain respectively is dissolved in water, make the solution that every 1ml contains the about 30mg of nimesulide, get solution 0.8ml adding chromatography respectively and live the top, with phosphate buffer 50ml eluting, flow velocity 1.3ml/min, the eluent of collecting adds rupture of membranes agent (ethanol: 50ml benzyl alcohol=6: 1), mixing, the content M of high performance liquid chromatography detection nimesulide
1
Envelop rate %=M
1/ M * 100%.
Table 1 entrapment efficiency determination result
By above result as can be known, the liposome encapsulation that proportioning makes of writing out a prescription of the embodiment in the scope of the invention is very high, meets the actual production requirement substantially; And the liposome encapsulation that the outer Comparative Examples prescription proportioning of the scope of the invention makes is very low, has compared tangible gap with embodiment, is not suitable for production requirement.
The detection of test example 2 particle diameters
Get the liposome of embodiment 1-2 and Comparative Examples 1-2 preparation, adopt micro-image analyzer to measure the particle size distribution of liposome, result such as table 2:
Table 2 particle diameter testing result
By above result as can be known, the liposome that embodiment 1-2 makes shows spherical, ellipticity, and particle diameter is even, and scope is 80-200nm; The liposome shape that Comparative Examples 1-2 makes is indefinite, not of uniform size, and particle diameter is inhomogeneous, and scope is 300-900nm.
The detection of test example 3 dissolutions
Get Nimesulide liposome preparation and listing preparation nimesulide capsule (HaiNan Kangzhi Pharmaceutical Co., Ltd produces, lot number 20081118) that embodiment 4-8 makes, carry out dissolution respectively and detect, the result is as follows:
Table 3 dissolution testing result
By above result as can be known, the sample dissolution of embodiment of the invention 4-8 is higher than 78.3% of listing tablet far away all more than 90%, illustrates that the Nimesulide liposome that the present invention makes has improved its dissolubility, thereby has improved bioavailability accordingly.
Should be appreciated that these embodiment only are the explanations to preferred version of the present invention, and also limit protection scope of the present invention never in any form.Those skilled in the art under the prerequisite that does not deviate from the present invention's spirit and purport, can carry out suitable modification and improvement to the present invention under the instruction of the disclosed content of the present invention, these all will fall within the scope of the present invention.
Claims (9)
1, a kind of nimesulide liposome solid preparation is made up of nimesulide and acceptable accessories, it is characterized in that making nimesulide liposome solid preparation with other adjuvants again after nimesulide is made liposome.
2, nimesulide liposome solid preparation according to claim 1, wherein said liposome is made by following parts by weight of component: 1 part of nimesulide, 3～10 parts of glycerol monolaurate, 0.5～4 part in cholesterol, 1880.1～2 parts of poloxamers.
3, nimesulide liposome solid preparation according to claim 2, wherein said liposome can also comprise the pharmaceutically acceptable buffer salt solution of regulating pH value to 5.5～6.5, and for example buffer salt solution is selected from one or more in phosphate buffer, citrate buffer, carbonate buffer solution, borate buffer solution, the acetate buffer.
4, nimesulide liposome solid preparation according to claim 3, wherein said liposome is to make by the method that comprises the steps: (1) is dissolved in nimesulide, glycerol monolaurate, cholesterol and poloxamer 188 in the organic solvent, mix homogeneously makes immobilized artificial membrane after organic solvent is removed in decompression; (2) add buffer salt solution and make the complete aquation of immobilized artificial membrane, even matter emulsifying makes liposome turbid liquor; (3) with liposome turbid liquor lyophilization or spray drying, make Nimesulide liposome.
5, nimesulide liposome solid preparation according to claim 4, wherein said organic solvent is selected from one or more in ethanol, chloroform, methanol, the tert-butyl alcohol, n-butyl alcohol, isopropyl alcohol, acetone, ether, benzyl alcohol, the normal hexane.
6, according to the described nimesulide liposome solid preparation of claim 1-5, it is characterized in that making: Nimesulide liposome 5%-40%, diluent 10%-60% by following components in weight percentage, disintegrating agent 1%-5%, binding agent 0.5%-5%, correctives 0%-20%, lubricant 0%-5%.
7, according to the described nimesulide liposome solid preparation of claim 1-6, wherein:
Described diluent is selected from one or more in microcrystalline Cellulose, starch, pregelatinized Starch, lactose, sorbitol, mannitol, dextrin, calcium sulfate, the calcium hydrogen phosphate; Perhaps
Described disintegrating agent is selected from one or more in carboxymethylstach sodium, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, the dried starch; Perhaps
Described binding agent is selected from one or more in 30 POVIDONE K 30 BP/USP 30, hypromellose, starch slurry, sodium carboxymethyl cellulose, the syrup; Perhaps
Described correctives is selected from one or more in sucrose, Aspartane, saccharin sodium, the steviosin; Perhaps described lubricant is selected from one or more in magnesium stearate, Pulvis Talci, colloidality silicon dioxide, PEG6000, the sodium lauryl sulphate etc.
8,, it is characterized in that it is granule, tablet, capsule, dispersible tablet or dry suspension according to the described nimesulide liposome solid preparation of claim 1-7.
9, the preparation method of the described nimesulide liposome solid preparation of claim 1-8, it comprises the steps:
(1) Nimesulide liposome is pulverized, crossed 80 mesh sieves, standby;
(2) get diluent, disintegrating agent and correctives, cross 80 mesh sieves, mix, standby;
(3) with above-mentioned supplementary material mix homogeneously, add binder solution system soft material, the granulation of sieving, oven dry, the adding mix lubricant is even, and granulate gets the nimesulide granule;
(4) granule is carried out packing or tabletting, make nimesulide liposome solid preparation.
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| CN2009101469472A CN101642433B (en) | 2009-06-08 | 2009-06-08 | Nimesulide liposome solid preparation and preparation method of drug composite thereof |
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| CN2009101469472A CN101642433B (en) | 2009-06-08 | 2009-06-08 | Nimesulide liposome solid preparation and preparation method of drug composite thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102188364A (en) * | 2010-03-18 | 2011-09-21 | 鲁翠涛 | Preparation method of drug-carrying lipoid particles |
| CN102232928A (en) * | 2010-04-20 | 2011-11-09 | 广州艾格生物科技有限公司 | Nimesulide sustained-release suspension and preparation method thereof |
-
2009
- 2009-06-08 CN CN2009101469472A patent/CN101642433B/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102188364A (en) * | 2010-03-18 | 2011-09-21 | 鲁翠涛 | Preparation method of drug-carrying lipoid particles |
| CN102188364B (en) * | 2010-03-18 | 2016-01-20 | 浙江海正药业股份有限公司 | The preparation method of medicament-carrying lipoid particulates |
| CN102232928A (en) * | 2010-04-20 | 2011-11-09 | 广州艾格生物科技有限公司 | Nimesulide sustained-release suspension and preparation method thereof |
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| CN101642433B (en) | 2011-08-24 |
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