CN101536990A - Colchicines gastric floating sustained-release tablet and method for preparing same - Google Patents
Colchicines gastric floating sustained-release tablet and method for preparing same Download PDFInfo
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- CN101536990A CN101536990A CN200810065894A CN200810065894A CN101536990A CN 101536990 A CN101536990 A CN 101536990A CN 200810065894 A CN200810065894 A CN 200810065894A CN 200810065894 A CN200810065894 A CN 200810065894A CN 101536990 A CN101536990 A CN 101536990A
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Abstract
The invention discloses a colchicines gastric floating sustained-release tablet, which comprises active components of colchicines and pharmaceutic adjuvant according to the weight ratio of 1:24-1,999, wherein the pharmaceutic adjuvant comprises a hydrophilic gel framework material, a effervescing agent, a floating assistant material, a filler, a pH value regulator and a lubricant. The colchicines gastric floating sustained-release tablet can swell quickly in gastric juice or a similar gastric juice medium and can float on the gastric juice for at least 4 hours. The invention also relates to a method for preparing the colchicines gastric floating sustained-release tablet. The colchicines gastric floating sustained-release tablet can reach the effective blood-drug concentration quickly after being taken and then release drugs slowly, and can maintain the balanced blood-drug concentration so as to reduce the dose times, relieve the toxic side effect and improve the bioavailability.
Description
Technical field
The present invention relates to a kind of medicine that contains the colchicine composition and preparation method thereof, relate in particular to a kind of Colchicines gastric floating preparation and preparation method thereof.
Background technology
Colchicine (colchicine) is a kind of Tropolones alkaloid, separates the bulb from the liliaceous plant Colchicum autumnale Colchicum autumnale L. in Europe the earliest.Colchicine has significant biological activity, mainly contain pharmacological actions such as antiinflammatory, antitumor, fibrosis, be used for the treatment of gout, various malignant tumor clinical more, studies show that in recent years it also has curative effect preferably to family's Mediterranean fruit fly, liver cirrhosis, hepatitis gravis, recurrent pericarditis, BechetShi disease etc.Wherein, colchicine was the specific drug of treatment gout acute attack, just was used for the treatment of the outbreak of gout as far back as 1763, was still main medicine so far.
But there is such shortcoming in prior art: promptly the toxicity of colchicine is bigger, and the clinical therapeutic index that is used for the treatment of gout is little, and (treatment window blood drug level is 0.5～3ng/ml).The absorption window of finding colchicine after deliberation is also narrower, and it is relatively poor in absorption of small intestinal upper end absorption of rear end better and in intestinal.
Present document is not seen the record of relevant Colchicines gastric floating preparation as yet.In order to overcome conventional tablet and the big drawback of capsule toxic and side effects, need be made into sustained-release preparation; The open gastric retention type slow releasing preparation of the present invention, solved its problem that oral absorption window is narrow, bioavailability is low, to reach control drug release and then to obtain more stable blood drug level, reduce gastrointestinal side effect, improve drug bioavailability simultaneously, be convenient to the purpose of medication.
Summary of the invention
The technical problem to be solved in the present invention be to provide a kind of can reach rapidly effective blood drug concentration, then slowly release keep blood drug level steadily, reduce medicining times, alleviate toxic and side effects, Colchicines gastric floating sustained-release tablet that bioavailability is high, to overcome the deficiency of existing product.
Another technical problem that the present invention will solve is that a kind of preparation method of Colchicines gastric floating sustained-release tablet is provided.
For solving the problems of the technologies described above, the technical scheme that the present invention takes is such:
A kind of Colchicines gastric floating sustained-release tablet of the present invention, comprise active component colchicine and pharmaceutic adjuvant, the weight proportion of described active component colchicine and pharmaceutic adjuvant is 1: 24～1999, include hydrophilic gel matrix material, effervescent in the described pharmaceutic adjuvant and help and float material, described Colchicines gastric floating sustained-release tablet swelling rapidly under gastric juice or similar gastric juice medium, and may float on the gastric juice at least 4 hours, reach and continue slow release and keep blood drug level effect stably.
The pharmaceutic adjuvant of Colchicines gastric floating sustained-release tablet of the present invention also can further comprise filler, pH value regulator, lubricant.
Colchicines gastric floating sustained-release tablet of the present invention comprises following components in weight percentage:
Colchicine 0.05-4%;
Hydrophilic gel matrix material 6.67-53.33%;
Effervescent 3.33-20%;
Help and float material 6.67-33.33%;
Filler 6.67-66.67%;
PH value regulator 3.33-20%;
Lubricant 0.33-3.33%.
Described hydrophilic gel matrix material is selected from a kind of or combination in polyethylene glycol oxide, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, polyvinylacetate, sodium alginate, carrageenan, carbomer, the hydroxypropyl cellulose; Effervescent is selected sodium bicarbonate, calcium carbonate or magnesium carbonate for use; Help and float material selection stearic acid, glyceryl monostearate, Cera Flava, polyacrylic resin; Filler is selected microcrystalline Cellulose, lactose, starch, glucose, sucrose, mannitol, calcium hydrogen phosphate, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium or ethyl cellulose for use; The pH value regulator is selected citric acid, tartaric acid for use.
As a preferred embodiment, in Colchicines gastric floating sustained-release tablet of the present invention, described hydrophilic gel matrix material is selected from polyethylene glycol oxide; Effervescent is selected sodium bicarbonate for use; Help and float the material selection polyacrylic resin; Filler is selected microcrystalline Cellulose for use; The pH value regulator is selected citric acid for use.
As a specific embodiment, described Colchicines gastric floating sustained-release tablet comprises following components in weight percentage:
Colchicine 0.05-4%;
Polyethylene glycol oxide-WSR303 6.67-53.33%;
Sodium bicarbonate 3.33-20%;
You Teqi L100-55 6.67-33.33%;
Microcrystalline Cellulose 6.67-66.67%;
Citric acid 3.33-20%;
Magnesium stearate 0.33-3.33%.
The present invention's scheme of preferably filling a prescription: described Colchicines gastric floating sustained-release tablet comprises following components in weight percentage:
Colchicine 0.67%;
Polyethylene glycol oxide-WSR303 20%;
You Teqi L100-55 16.67%;
Microcrystalline Cellulose 43.67%;
Citric acid 7.67%;
Iron oxide red 0.33%;
The preparation method of Colchicines gastric floating sustained-release tablet of the present invention may further comprise the steps:
A. colchicine and hydrophilic gel matrix material, effervescent, bleach activator, filler, pH value regulator and lubricant are pressed equivalent incremental method mix homogeneously;
B. carry out direct powder compression.
The tablet machine punch die is a dimple form among the step b, Φ=7mm; Label hardness 35-45N, the heavy 150mg of sheet ± 2%.
Compared with prior art, the present invention has following advantage and technique effect: can reach effective blood drug concentration, slowly release then after this preparation is taken rapidly, can keep, thereby can reduce medicining times, alleviate toxic and side effects, improve bioavailability than stable blood concentration.
Brief Description Of Drawings
Fig. 1 is preparation technology's general flow chart of Colchicines gastric floating sustained-release tablet of the present invention;
Fig. 2 is the influence of Colchicines gastric floating sustained-release tablet different amounts effervescent of the present invention to the matrix tablet release;
Fig. 3 is the influence of Colchicines gastric floating sustained-release tablet different amounts polyethylene glycol oxide WSR303 of the present invention to the matrix tablet release;
Fig. 4 is the influence of the strange L100-55 of Colchicines gastric floating sustained-release tablet different amounts You Te of the present invention to the matrix tablet release;
Fig. 5 is the influences of the different filler types of Colchicines gastric floating sustained-release tablet of the present invention to the matrix tablet release;
Fig. 6 is the influences of the different tabletting hardness of Colchicines gastric floating sustained-release tablet of the present invention to the matrix tablet release;
Fig. 7 is the influences of the different tablet profiles of Colchicines gastric floating sustained-release tablet of the present invention to the matrix tablet release;
Fig. 8 is the release profiles of the uniform Design prescription of Colchicines gastric floating sustained-release tablet of the present invention;
Fig. 9 is the Colchicines gastric floating sustained-release tablet release in vitro of the present invention line of writing music;
Figure 10 is the corrosion curve of Colchicines gastric floating sustained-release tablet of the present invention;
Figure 11 concerns between the corrosion percentage rate of Colchicines gastric floating sustained-release tablet of the present invention and the cumulative release rate;
Curve chart when Figure 12 is the medicine of colchicine ordinary tablet and intragastric floating tablets.
The specific embodiment
The formulating process, the parameter that specifically describe Colchicines gastric floating sustained-release tablet of the present invention are below selected foundation, and enumerate specific embodiment and further specify technical scheme of the present invention:
The Gastroretentive formulations technical development methods such as stomach floating system, gastric expansion system, bioadhesion system, location, magnetic field occurred so far, and is wherein ripe with the stomach flotation technique.What adopt is principle according to water balance kinetics (HBS) and the stomach flotation technique is most, and the preparation hydrogel matrix tablet utilizes the hydrogel material molecular weight big, and hydration rate is slow, and the characteristics that the flotation property of generation is good reach buoyant effect.
1. instrument and reagent
Colchicine (060110, Yunnan Ban Na Pharmaceutical Co., Ltd, purity is greater than 98%)
Yellow ferric oxide (20061102, Shanghai Yipin Pigments Co., Ltd.)
Polyoxyethylene (Polyox WSR303, TAO0355S5R3, U.S. DOW company)
Sodium bicarbonate (Tianjin red rock chemical reagent factory, 20070405)
Citric acid (Tianjin red rock chemical reagent factory, 20050506)
You Teqi (the strange L100-55 of You Te, B060504017, U.S. ROHM company)
Microcrystalline Cellulose (Avicel PH102, U.S. FMC Corp.)
Magnesium stearate (20030215, big forever chemical reagent center, Tianjin, A.R)
TDP single punch tablet machine (Tianxiang Jiantai Pharmaceutical Machinery Co., Ltd., Shanghai)
YD-20 intelligence tablet hardness instrument (the huge unlimited power plant in Tianjin)
ZRS-8G type intelligence digestion instrument (Radio Factory of Tianjin Univ.)
You Teqi (You Teqi) is the trade name of known synthetic pharmaceutic adjuvant that this area has now, and it comprises methacrylic acid copolymer and methacrylate copolymer, is called acrylic resin the old China hand; You Teqi is widely used in the skeleton adhesive material of the gastric solubleness coating, enteric coating of medicine agent, slow controlled release coat, protection isolation coat, sustained-release matrix material and percutaneous drug administration preparation; Wherein the chemical composition of the strange L 100-55 of You Te is: methacrylic acid and ethyl acrylate (1: 1) copolymer.
The kind of You Teqi product such as following table:
* represents to obtain SFDA import drugs registration certificate in the last table; △ represents to register
2. Colchicines gastric floating sustained-release tablet is write out a prescription and technical study
Preparation technology's flow process of Colchicines gastric floating sustained-release tablet sees for details shown in Figure 1.
With reference to pertinent literature report and preliminary experiment result, the present invention adopts similar factors method (f
2) as evaluation index, investigate the influence of prescription component and preparation process to the Colchicine framework controlled release tablets drug release behavior.
The basic prescription that adopts in the experimentation is as follows:
| Colchicine (Colchicine) | 0.5-5.0mg preferred 1.0mg |
| Iron oxide red (Ferric oxide) | 0.1-1.0mg preferred 0.5mg |
| Polyoxyethylene (POLYOX WSR303) | 10.0-50.0mg preferred 30.0mg |
| You Teqi (the strange L100-55 of You Te) | 10.0-50.0mg preferred 25.0mg |
| Sodium bicarbonate (NaHCO 3) | 5.0-30.0mg preferred 15.0mg |
| Citric acid (Citric acid) | 5.0-30.0mg preferred 11.5mg |
| Microcrystalline Cellulose (MCC) | 10.0-100.0mg preferred 65.5mg |
| Magnesium stearate (Mg-S) | 0.5-5.0mg preferred 1.5mg |
| Amount to | 41.1-270mg preferred 150mg |
Example one
Except that specifying, the technique for fixing parameter is as follows in the experimentation: adopt the equivalent incremental method with the supplementary material mixing, carry out direct powder compression.The tablet machine punch die is dimple form (Φ=7mm); Label hardness 35-45N, the heavy 150mg of sheet ± 2%.
External release condition: little agar diffusion method, with the 0.1molL of 200mL
-1HCl is the release medium, oar rotating speed 100rmin
-1, 37 ℃ of medium temperatures.
Single factor is investigated 2.1 write out a prescription
2.1.1 the effervescent consumption is to the influence of drug release behavior
The usage ratio of the consumption of other component and effervescent sodium bicarbonate and citric acid in the fixed prescription is adjusted effervescent shared ratio in prescription, and substitutes with the equivalent microcrystalline Cellulose, and investigation effervescent consumption is to the influence of drug release behavior.
The f of the different effervescent consumptions of table 1
2The factor relatively
Measure the release that swims in 12 hours according to the drug release determination method, the results are shown in Table 1 and Fig. 2, whether the existence that shows effervescent has appreciable impact to drug release, but effervescent consumption (prescription total amount 5%～20%) in the scope of being investigated does not then have obvious influence to drug release behavior.
2.1.2 hydrophilic gel matrix material polyethylene glycol oxide WSR303 consumption is to the influence of drug release behavior
The consumption of other component in the fixed prescription is adjusted polyethylene glycol oxide WSR303 shared ratio in prescription, and substitutes with the equivalent microcrystalline Cellulose, and investigation polyethylene glycol oxide WSR303 consumption is to the influence of drug release behavior.
The f of the different polyethylene glycol oxide WSR303 of table 2 consumption
2The factor relatively
Measure the release swim in 12 hours according to the drug release determination method, the results are shown in Table 2 and Fig. 3, show that polyethylene glycol oxide WSR303 consumption has appreciable impact to drug release.
2.1.3 the strange L100-55 consumption of You Te is to the influence of drug release behavior
The consumption of other component in the fixed prescription is adjusted the strange L100-55 of You Te shared ratio in prescription, and substitutes with the equivalent microcrystalline Cellulose, and the strange L100-55 consumption of investigation You Te is to the influence of drug release behavior.
The f of the strange L100-55 consumption of the different You Te of table 3
2The factor relatively
Measure the release swim in 12 hours according to the drug release determination method, the results are shown in Table 3 and Fig. 4, show that the strange L100-55 consumption of You Te has appreciable impact to drug release.
2.1.4 the filler type is to the influence of drug release behavior
The consumption of each component in the fixed prescription, the kind of filler in the change prescription is investigated the influence of filler type to drug release behavior.
The f of the different filler types of table 4
2The factor relatively
Measure the release swim in 12 hours according to the drug release determination method, the results are shown in Table 4 and Fig. 5, show that the filler type has appreciable impact to drug release.
2.2 the single factor of technology is investigated
2.2.1 tabletting hardness is to the influence of drug release behavior
Fixed prescription is formed and other process conditions, adjusts tabletting hardness, investigates the influence of hardness to drug release behavior.
The f of the different tabletting hardness of table 5
2The factor relatively
Measure the release of floating tablets in 12 hours according to the drug release determination method, the results are shown in Table 5 and Fig. 6, show that tabletting hardness do not have obvious influence to drug release.
2.2.2 the tablet profile is to the influence of drug release behavior
Fixed prescription is formed and other process conditions, adjusts the compression mold diameter, investigates the influence of tablet overall dimensions to drug release behavior.
The f of the different tablet external forms of table 6
2The factor relatively
Measure the release of floating tablets in 12 hours according to the drug release determination method, the results are shown in Table 6 and Fig. 7, show that the tablet profile diameter do not have obvious influence to drug release.
3. release mechanism research
3.1 floating and effect status corrosion mechanism
3.1.1 the effect of floating mechanism
3.1.1.1 the influence of effervescent
The usage ratio of the consumption of other component and effervescent sodium bicarbonate and citric acid in the fixed prescription, adjust effervescent shared ratio in prescription, and alternative with the equivalent microcrystalline Cellulose, investigate of the influence of effervescent consumption to working the time of floating and holding the time of floating, rate of releasing drug.
Table 8 effervescent consumption is to floating and influence drug release behavior
| Prescription | Effervescent/mg | T lag(s) | T f(h) | Rate of releasing drug/ |
| 1 | 0％ | / | 0 | 8.44 |
| 2 | 5％ | 5 | ＞12 | 4.90 |
| 3 | 10％ | 4 | ＞12 | 4.90 |
| 4 | 15％ | 3 | ＞12 | 4.79 |
| 5 | 20％ | 1 | ＞12 | 4.23 |
Measure the release of floating tablets in 12 hours according to the drug release determination method, the results are shown in Table 8, the have unmatchful flotation property and the rate of releasing drug of effervescent influence significantly.Along with the increase of effervescent consumption, the tablet flotation property strengthens (rise and float the time shortening), rate of releasing drug has the trend of slowing down, but influences not obvious.
3.1.1.2 lightweight helps the influence of floating material
The consumption of other component in the fixed prescription is adjusted lightweight and is helped and float the strange L100-55 of material You Te shared ratio in prescription, and substitutes with the equivalent microcrystalline Cellulose, investigates the influence of the strange L100-55 consumption of You Te to working the time of floating and holding the time of floating, rate of releasing drug.
The strange L100-55 consumption of table 9 You Te is to floating and influence drug release behavior
| Prescription | You Teqi L100-55/mg | T lag(s) | T f(h) | Rate of releasing drug/ |
| 1 | 0％ | 4 | ＞12 | 9.79 |
| 2 | 10％ | 4 | ＞12 | 5.72 |
| 3 | 20％ | 6 | ＞12 | 4.24 |
| 4 | 30％ | 3 | ＞12 | 3.69 |
| 5 | 40％ | 2 | ＞12 | 3.92 |
Measure the release of floating tablets in 12 hours according to the drug release determination method, the results are shown in Table 9, the consumption of the strange L100-55 of You Te does not make significant difference to flotation property, but rate of releasing drug significantly reduces with the increase of its consumption.
3.1.1.3 the influence of hydrophilic gel matrix material
The consumption of other component in the fixed prescription, adjust hydrophilic gel matrix material polyethylene glycol oxide WSR303 shared ratio in prescription, and alternative with the equivalent microcrystalline Cellulose, investigate of the influence of polyethylene glycol oxide WSR303 consumption to working the time of floating and holding the time of floating, rate of releasing drug.
Table 10 polyethylene glycol oxide WSR303 consumption is to floating and influence drug release behavior
Measure the release of floating tablets in 12 hours according to the drug release determination method, the results are shown in Table 10, the consumption of polyethylene glycol oxide WSR303 does not make significant difference to flotation property, but initial release amount significantly reduces with the increase of its consumption, the stable state rate of releasing drug then has reduction slightly.But polyethylene glycol oxide WSR303 is the skeleton backing material of whole system, and lacking then can not molding.
3.1.2 the effect of corrosion mechanism
Adopt release in vitro degree method for measuring and condition, Colchicines gastric floating sustained-release tablet is stirred 2,4,6,8,10, takes out behind the 12h in water, put 60 ℃ of dry 24h in the baking oven, weigh.According to former re-computation weight loss percentage, be the corrosion percentage rate.
With the corrosion percentage rate time is mapped, the results are shown in Figure 10.Its equation of linear regression is: E=4.4691t+5.3125 (r=0.9962).Show that tablet then at the uniform velocity corrosion, erosion rate behind 2h are that slope of a curve is 4.4691h
-1To the mapping of corrosion percentage rate, the results are shown in Figure 11 with the cumulative release rate.Its regression equation is: M
t=59.866lnt-143.3 (r=0.9923).Show that drug release and its corrosion behavior are synchronous, but be subjected to the influence of flooding mechanism simultaneously.
3.2 fitting of external release model
The release model match table of table 11 Colchicines gastric floating sustained-release tablet
| Model | Equation | Coefficient R |
| Zero order | y＝7.5158t-+14.723 | 0.986 |
| First order | log(100-y)＝-0.1262t+2.1655 | 0.974 |
| Higuchi | y＝13.292t 1/2-38.413 | 0.9923 |
According to the Peppas equation, for cylindrical preparation, the index n of time t can be used to describe release mechanism.The n value of this test equation match is 0.72, illustrates that drug release is non-Fick diffusion; In conjunction with above experimental result, show that this preparation drug release process is the coefficient result of drug diffusion and bulk erosion.
Pharmacokinetic studies in the 4 Beagle dog bodies
Give commercially available ordinary tablet of Beagle dog colchicine (every 0.5mg, totally 2) and Colchicines gastric floating sustained-release tablet (every 1.0mg, totally 1) respectively, get blood respectively and adopt the LC-MS method to measure blood drug level.Record drug-time curve as shown in figure 12, the main pharmacokinetic parameters of calculating and two kinds of dosage forms of comparison sees Table 12.The result shows, less and long period of intragastric floating tablets blood concentration fluctuation maintains in the treatment window scope, safer effectively.Curve chart is seen Figure 12 during the medicine of colchicine ordinary tablet and intragastric floating tablets.
The main pharmacokinetic parameters of table 12 colchicine ordinary tablet and intragastric floating tablets
| Parameter | Intragastric floating tablets | Ordinary tablet |
| Tmax(h) | / | 1.5 |
| Cmax(ng/ml) | 2.05 | 6.84 |
| AUC | 22.60 | 23.56 |
Sum up and conclude above-mentioned experimental result, obtain the following specific embodiment of Colchicines gastric floating sustained-release tablet of the present invention:
Embodiment 1:
| The component title | Prescription |
| Colchicine | 10g |
| Iron oxide red | 5g |
| Polyoxyethylene WSR303 | 300g |
| You Teqi L100-55 | 250g |
| Sodium bicarbonate | 150g |
| Citric acid | 115g |
| Microcrystalline Cellulose | 655g |
| Magnesium stearate | 15g |
| Amount to | 1500g |
Preparation method:
A. colchicine and polyethylene glycol oxide WSR303, sodium bicarbonate, the strange L100-55 of You Te, microcrystalline Cellulose, citric acid and iron oxide red, magnesium stearate are pressed equivalent incremental method mix homogeneously;
B. carry out direct powder compression, the tablet machine punch die is a dimple form, Φ=7mm; Label hardness 35-45N, the heavy 150mg of sheet ± 2%.
Embodiment 2:
| The component title | Prescription |
| Colchicine | 0.75g |
| Iron oxide red | 10g |
| Hydroxypropyl emthylcellulose | 799.95g |
| You Teqi L100-55 | 100g |
| Sodium bicarbonate | 50g |
| Citric acid | 50g |
| Microcrystalline Cellulose | 484.3g |
| Magnesium stearate | 5g |
| Amount to | 1500g |
Preparation method:
A. colchicine and hydroxypropyl emthylcellulose, sodium bicarbonate, the strange L100-55 of You Te, microcrystalline Cellulose, citric acid and iron oxide red, magnesium stearate are pressed equivalent incremental method mix homogeneously;
B. carry out direct powder compression, the tablet machine punch die is a dimple form, Φ=7mm; Label hardness 35-45N, the heavy 150mg of sheet ± 2%.
Embodiment 3:
| The component title | Prescription |
| Colchicine | 60g |
| Iron oxide red | 1g |
| Polyoxyethylene WSR303 | 100g |
| You Teqi L100-55 | 500g |
| Calcium carbonate | 300g |
| Citric acid | 300g |
| Microcrystalline Cellulose | 189g |
| Magnesium stearate | 50g |
| Amount to | 1500g |
Preparation method:
A. colchicine and polyethylene glycol oxide WSR303, calcium carbonate, the strange L100-55 of You Te, microcrystalline Cellulose, citric acid and iron oxide red, magnesium stearate are pressed equivalent incremental method mix homogeneously;
B. carry out direct powder compression, the tablet machine punch die is a dimple form, Φ=7mm; Label hardness 35-45N, the heavy 150mg of sheet ± 2%.
Embodiment 4:
| The component title | Prescription |
| Colchicine | 10g |
| Iron oxide red | 5g |
| Polyoxyethylene WSR303 | 763g |
| Polyacrylic resin | 300g |
| Sodium bicarbonate | 200g |
| Citric acid | 110g |
| Lactose | 100g |
| Magnesium stearate | 12g |
| Amount to | 1500g |
Preparation method:
A. colchicine and polyethylene glycol oxide WSR303, sodium bicarbonate, polyacrylic resin, lactose, citric acid and iron oxide red, magnesium stearate are pressed equivalent incremental method mix homogeneously;
B. carry out direct powder compression, the tablet machine punch die is a dimple form, Φ=7mm; Label hardness 35-45N, the heavy 150mg of sheet ± 2%.
Embodiment 5:
| The component title | Prescription |
| Colchicine | 10g |
| Iron oxide red | 10g |
| Polyoxyethylene WSR303 | 185g |
| You Teqi L100-55 | 120g |
| Sodium bicarbonate | 80g |
| Citric acid | 90g |
| Microcrystalline Cellulose | 1000g |
| Magnesium stearate | 5g |
| Amount to | 1500g |
Preparation method:
A. colchicine and polyethylene glycol oxide WSR303, sodium bicarbonate, the strange L100-55 of You Te, microcrystalline Cellulose, citric acid and iron oxide red, magnesium stearate are pressed equivalent incremental method mix homogeneously;
B. carry out direct powder compression, the tablet machine punch die is a dimple form, Φ=7mm; Label hardness 35-45N, the heavy 150mg of sheet ± 2%.
Claims (9)
1. Colchicines gastric floating sustained-release tablet, comprise active component colchicine and pharmaceutic adjuvant, it is characterized in that: the weight proportion of described active component colchicine and pharmaceutic adjuvant is 1: 24～1999, includes hydrophilic gel matrix material, effervescent in the described pharmaceutic adjuvant and helps and float material.
2. Colchicines gastric floating sustained-release tablet according to claim 1 is characterized in that: described pharmaceutic adjuvant also further comprises filler, pH value regulator, lubricant.
3. Colchicines gastric floating sustained-release tablet according to claim 1 is characterized in that: described Colchicines gastric floating sustained-release tablet comprises following components in weight percentage:
Colchicine 0.05-4%;
Hydrophilic gel matrix material 6.67-53.33%;
Effervescent 3.33-20%;
Help and float material 6.67-33.33%;
Filler 6.67-66.67%;
PH value regulator 3.33-20%;
Lubricant 0.33-3.33%.
4. according to claim 2 or 3 described Colchicines gastric floating sustained-release tablets, it is characterized in that: described hydrophilic gel matrix material is selected from a kind of or combination in polyethylene glycol oxide, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, polyvinylacetate, sodium alginate, carrageenan, carbomer, the hydroxypropyl cellulose; Described effervescent is selected sodium bicarbonate, calcium carbonate or magnesium carbonate for use; Described helping floated material selection stearic acid, glyceryl monostearate, Cera Flava, polyacrylic resin; Described filler is selected microcrystalline Cellulose, lactose, starch, glucose, sucrose, mannitol, calcium hydrogen phosphate, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium or ethyl cellulose for use; Described pH value regulator is selected citric acid, tartaric acid for use.
5. according to claim 2 or 3 described Colchicines gastric floating sustained-release tablets, it is characterized in that: described hydrophilic gel matrix material is selected from polyethylene glycol oxide; Described effervescent is selected sodium bicarbonate for use; Described helping floated the material selection polyacrylic resin; Described filler is selected microcrystalline Cellulose for use; Described pH value regulator is selected citric acid for use.
6. Colchicines gastric floating sustained-release tablet according to claim 1 and 2 is characterized in that: this intragastric floating tablets comprises following components in weight percentage:
Colchicine 0.05-4%;
Polyethylene glycol oxide-WSR303 6.67-53.33%;
Sodium bicarbonate 3.33-20%;
You Teqi L100-55 6.67-33.33%;
Microcrystalline Cellulose 6.67-66.67%;
Citric acid 3.33-20%;
Magnesium stearate 0.33-3.33%.
7. Colchicines gastric floating sustained-release tablet according to claim 6 is characterized in that: this intragastric floating tablets comprises following components in weight percentage:
Colchicine 0.67%;
Polyethylene glycol oxide-WSR303 20%;
Sodium bicarbonate 10%;
You Teqi L100-55 16.67%;
Microcrystalline Cellulose 43.66%;
Citric acid 7.67%;
Iron oxide red 0.33%;
Magnesium stearate 1%.
8. the preparation method of a Colchicines gastric floating sustained-release tablet is characterized in that may further comprise the steps:
A. colchicine and hydrophilic gel matrix material, effervescent, bleach activator, filler, pH value regulator and lubricant are pressed equivalent incremental method mix homogeneously;
B. carry out direct powder compression.
9. the preparation method of Colchicines gastric floating sustained-release tablet as claimed in claim 8, it is characterized in that: the tablet machine punch die is a dimple form among the described step b, Ф=7mm; Label hardness 35-45N, the heavy 150mg of sheet ± 2%.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810065894A CN101536990A (en) | 2008-03-18 | 2008-03-18 | Colchicines gastric floating sustained-release tablet and method for preparing same |
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|---|---|---|---|
| CN200810065894A CN101536990A (en) | 2008-03-18 | 2008-03-18 | Colchicines gastric floating sustained-release tablet and method for preparing same |
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| Publication Number | Publication Date |
|---|---|
| CN101536990A true CN101536990A (en) | 2009-09-23 |
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| CN200810065894A Pending CN101536990A (en) | 2008-03-18 | 2008-03-18 | Colchicines gastric floating sustained-release tablet and method for preparing same |
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| CN112245399A (en) * | 2020-10-29 | 2021-01-22 | 西南医科大学 | Dihydromyricetin gastric floating pill and preparation method thereof |
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- 2008-03-18 CN CN200810065894A patent/CN101536990A/en active Pending
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| CN112933055A (en) * | 2021-03-23 | 2021-06-11 | 深圳前海九华国际投资控股有限公司 | Paliperidone gastric retention tablet and preparation method thereof |
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