CN102988181A - Granulating method and application for oral solid preparation - Google Patents
Granulating method and application for oral solid preparation Download PDFInfo
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- CN102988181A CN102988181A CN2012105878653A CN201210587865A CN102988181A CN 102988181 A CN102988181 A CN 102988181A CN 2012105878653 A CN2012105878653 A CN 2012105878653A CN 201210587865 A CN201210587865 A CN 201210587865A CN 102988181 A CN102988181 A CN 102988181A
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Abstract
The invention relates to a granulating method and application for an oral solid preparation and suitable to pharmaceutical companies. A material of a low melting point is heated and is melted to the liquid, the material is sprayed to a material of which the freezing point temperature is lower than the material or the mixture and which is in the dynamic state, the material of the low melting point is frozen, the material is bonded into granules, prepared granules are uniform, the flow performance is good, and the prepared granules serve as the intermediate of prepared pieces, capsules, granular agents and suspension. According to the method, a solution is not used, the energy consumption is low, the pollution is low, the problems that the environment is polluted caused by the fact that the energy consumption is high and the organic solvent is volatilized due to the solution (water, various organic solvents, the mixing solvent of organic solvents or the mixing solvent of water and organic solvents) which is used in a wet granulating method are solved, the solvent is not used, the material is at the low temperature, the granules are formed, and the method is suitable to granulating of solvents or heat-unstable materials.
Description
Technical field
The present invention is a kind of method of granulating of novel solid preparation, more specifically says to be particularly suitable for solvent/or the granulation of determination system of thermal unstable material.
Background technology
Granulation is technique commonly used in the solid preparation, improves flowability, the mouldability of material by granulating, and improves the stability of medicine, controls the rate of release of medicine, covers the disagreeable taste of medicine, selects suitable prescription and technique, can achieve the above object; By the method for making classification wet method, dry method and fusion method are arranged.
Wet granulation is present the most frequently used method of granulating, but need to use a large amount of solvents, such as water, organic solvent such as ethanol etc., the aqueous solution of organic solvent or the mixed solution of organic solvent, and need under higher temperature, water or organic solvent volatilization to be removed, not only energy consumption is high, if with an organic solvent also can cause serious environmental pollution, but also may remain in the safety that affects medicine in the granule, and be not suitable for solvent and the unsettled medicine of high temperature, may also can produce crystal formation to polymorph medicine and make the transition, such as candesartan Cilexetil, affect the bioavailability of medicine.
Dry granulation is to adopt high-pressure extrusion that powder body is squeezed into first bulk or lamellar, then be ground into the granular size that needs, granule irregularity and granular size that present dry granulation is once made are inhomogeneous, fine powder is more, mobile undesirable, need repeatedly granulate, repeatedly screening, extruding is granulated and just can be obtained comparatively ideal granule repeatedly, efficient is lower, and be not suitable for the medicine that high-pressure extrusion can produce crystal formation transition, and dry granulation is not suitable for and need to covers the granulation that its disagreeable taste improves the medicine of mouthfeel by the granulation packaging medicine.
The present bibliographical information of melt granulation has two kinds of methods: first method is that low melting point and the even post-heating of other mixing of materials that need granulate are warming up to more than the melting temperature of this low melting point, and keep certain hour, make low melting point fusing and be attached on the material to be granulated, then cooling, the low melting point of melting solidifies and makes material granulating or bulk, then by method granulations such as granulate, this method at first requires low-melting-point material mass-energy even with mixing of materials to be granulated, therefore the granularity of low melting point there is higher requirement, tiny powder preferably, commercially available low melting point (pharmaceutic adjuvant) is bulk or lamellar mostly at present, pulverous less, application is restricted, in addition this method low melting point add large percentage the time, rear very difficult granulate is solidified in cooling, needs by cutting into granule; The second method is to add the medicine dissolution that needs granulation after the melting of low melting point heat temperature raising or to disperse wherein, then extrude or spray, cool off granulation by high temperature, this method need to be used more low melting point, can affect the release of medicine, reduces the bioavailability of medicine; And the method for above-mentioned two kinds of melt granulation all needs medicine and low melting point are heated to higher temperature (more than the fusing point of low melting point), and the time of high temperature is long, affects the stability of medicine, is not suitable for the granulation to the thermally labile medicine.
Summary of the invention
The method of granulating that the purpose of this invention is to provide a kind of novel oral solid formulation, prepared uniform particles, good fluidity, do not use solvent, energy consumption is low, and is pollution-free, and material is in lower temperature granulating, and this method of granulating is particularly suitable for the granulation to solvent and/or determination system of thermal unstable material.
Technical solution of the present invention is to adopt fluid bed granulator or turbine granulator; the fused solution atomizing of low melting point is sprayed on the medicine and the acceptable adjuvant mixed material of pharmacy of boiling; regulating inlet temperature remains on below the low melting point freezing point material; and be no more than 45 ℃, low melting point solidifies material is bonded into granule.
Low melting point among the present invention, refer to that fusing point is between 35 ~ 90 ℃, between preferred 40 ~ 80 ℃, include but not limited to Polyethylene Glycol, fatty acid, polyoxyl stearate, hydrogenated vegetable oil, castor oil hydrogenated, aliphatic alcohol, tristerin, behenic acid glyceride etc., can use separately, also can two or more mix use, the mass ratio of itself and material to be granulated at 1:25 between the 1:1.
Method of granulating provided by the invention is used for the granulation of oral drugs solid preparation.Atomizing after low melting point and/or the additive melting is sprayed on is lower than this material or mixture freezing point temperature and is in the dynamic material, low melting point and/or additive bind granulating in the material surface solidification with material.The present invention need not specific (special) requirements to the character of low melting point, and lamellar, granular, block, Fen Zhuan Zhuo can use, and the temperature of material is lower than the freezing point of low melting point, and is no more than 45 ℃, and material is in lower temperature all the time.The present invention combines the advantage of wet granulation and melt granulation, does not make water, organic solvent equal solvent, and the character of low melting point is not had specific (special) requirements, and the uniform particles that makes, good fluidity, and production efficiency is high; Method of granulating of the present invention is sprayed on the medicine of disagreeable taste after using non-water-soluble low melting point fusing, low melting point solidifies at medical surfaces, cover the disagreeable taste of medicine, and the more traditional melt granulation of the consumption of low melting point significantly reduces, and is little on the drug release impact; Pelletization Chinese medicine of the present invention is in lower temperature all the time, does not use solvent, and is especially suitable to heat and/or granulation unstable to wet (solvent) and/or that have polymorphic and/or need wrap up by granulating the medicine that improve the medicine mouthfeel.Be liquid after the low melting point melting of the present invention, with adhesive solution phase in the wet granulation seemingly, but do not need water or other solvent, so just avoided water or other solvent that medicine is exerted an adverse impact, and need not under higher temperature, to make solvent evaporates, energy savings not only, and pollute extremely low.And material is in lower temperature, has avoided medicine because standing the stability of long-time temperatures involved medicine, thereby has improved quality and the stability of medicine.
Advantage of the present invention is prepared uniform particles, and good fluidity does not use solvent, and energy consumption is low, and is pollution-free, and material is in lower temperature granulating, and this method of granulating is particularly suitable for the granulation to solvent and/or determination system of thermal unstable material.
This description has been listed the part example, but its range of application is not limited to these examples.
Example 1: candesartan cilexetil
One. prescription (1000 meters)
Candesartan Cilexetil 8g
Sodium chloride 90g
Carboxymethylstach sodium 5g
Polyethylene glycol 6000 8g
Magnesium stearate 1g
Two. preparation method
In the prescription ratio take by weighing polyethylene glycol 6000, be heated to 70 ~ 75 ℃, be fused into liquid (
).
2. the ratio in prescription takes by weighing respectively candesartan Cilexetil, sodium chloride, carboxymethylstach sodium mix homogeneously, add in the turbine granulator, and open turbine granulator, the control inlet temperature makes the material boiling, and temperature remains on 25 ~ 40 ℃, will (
) slowly be sprayed onto on the material by aerodynamic atomization, sprayed rear discharging, granulate, get the candesartan Cilexetil granule (
).
In the prescription ratio take by weighing magnesium stearate with (
) mix homogeneously, tabletting.
Three. 50 ℃ of accelerated stabilities are investigated
The candesartan cilexetil that makes in the embodiment of the invention and the Japanese Takede Chemical Industries Ltd product that gone on the market must the Loews sheet be placed under 50 ℃ of conditions and placed for 12 weeks, and with 0 o'clock testing result as 100% content, check its changes of contents situation, with the value (patent No. ZL93100008.4) of the embodiment of result and the contained optimum of document relatively, see Table 1.
50 ℃ of placements of table 1 candesartan cilexetil changes of contents situation that keeps sample
The candesartan cilexetil that table 1 data show makes by this law, its stability to significantly be better than Japanese Takede Chemical Industries Ltd gone on the market product must the Loews sheet.
Example 2: the candesartan Cilexetil amlodipine
One. prescription (1000 meters)
Candesartan Cilexetil 8g
Amlodipine Besylate Tablet 5g
Sodium chloride 80g
Cross-linked carboxymethyl cellulose sodium 7g
PEG 8000 4g
Magnesium stearate 1g
Two. preparation method
In the prescription ratio take by weighing PEG 8000, be heated to 70 ~ 80 ℃, be fused into liquid (
).
2. the ratio in prescription takes by weighing respectively candesartan Cilexetil, Amlodipine Besylate Tablet, sodium chloride, cross-linked carboxymethyl cellulose sodium mix homogeneously; add in the turbine granulator, open turbine granulator, the control inlet temperature makes the material boiling; temperature remains on 25 ~ 40 ℃, will (
) slowly be sprayed onto on the material by aerodynamic atomization, sprayed rear discharging, granulate, get candesartan Cilexetil amlodipine granule (
).
In the prescription ratio take by weighing magnesium stearate with (
) mix homogeneously, tabletting.
Three. the study on the stability of candesartan Cilexetil amlodipine
The related substance of table 2 candesartan Cilexetil Amlodipine sheet under 40 ℃, RH75% condition changes
Annotate:
★The candesartan Cilexetil amlodipine besylate tablets of military Tanabe Selyaku Co., Ltd listing
The data of table 2 show that its stability of tablet that the present invention prepares significantly is better than the candesartan Cilexetil amlodipine besylate tablets (Unisia) that military Tanabe Selyaku Co., Ltd goes on the market.
Example 3: Cefdinir capsule
One. prescription (1000 meters)
Cefdinir 100g
Carboxymethylstach sodium 10g
Sodium lauryl sulphate 0.5g
Polyoxyethylene stearate (40) ester 10g
Polyethylene glycol 6000 10g
Magnesium stearate 1g
Two. preparation method
In the prescription ratio take by weighing polyoxyethylene stearate (40) ester, polyethylene glycol 6000, be heated to 68 ~ 72 ℃, be fused into liquid (
).
2. the ratio in prescription takes by weighing respectively cefdinir, carboxymethylstach sodium, sodium lauryl sulphate mix homogeneously, add in the turbine granulator, and open turbine granulator, the control inlet temperature makes the material boiling, and temperature remains on 25 ~ 30 ℃, will (
) slowly be sprayed onto on the material by aerodynamic atomization, sprayed rear discharging, granulate, get the cefdinir granule (
).
In the prescription ratio take by weighing magnesium stearate with (
) mix homogeneously, filled capsules gets Cefdinir capsule.
Three. with the contrast of listing product
Table 3: with the contrast of listing product
At present both at home and abroad the Cefdinir capsule content of listing is Powdered, and poor fluidity press the cefdinir granule granule rounding of present embodiment preparation, and size evenly has excellent flowability, be suitable for minute encapsulated, and the height of the dissolution in water.
Cefdinir belongs to-lactam antibiotics, all unstable to water and heat, at present the method for granulating of the disclosed cefdinir preparation of document is to adopt water and ethanol as the wet granulation method of wetting agent, need in the manufacture process water, ethanol volatilized under higher temperature and remove, not only energy consumption is high, and can cause environmental pollution, and in drying course because temperature is higher, affect the stability of cefdinir.The present invention prepares the method for Cefdinir capsule, and medicine is under the lower temperature (room temperature) all the time, the decomposition of cefdinir when having avoided temperature higher, improved the stability of product, and do not used solvent, energy consumption is low, there is not pollutant emission, environmental protection.
Example 4: cefuroxime axetil for suspension
One. prescription (1000 bags of meters)
CEFUROXIME AXETIL 150g
Cross-linked carboxymethyl cellulose sodium (A) 16g
Sodium lauryl sulphate 1g
Micropowder silica gel 1g
Stearic acid 168g
Cross-linked carboxymethyl cellulose sodium (B) 40g
Sucrose 1500g
Xanthan gum 10g
Guar gum 10g
Polyethylene glycol 6000 100g
Aspartame 5g
Fructus Citri Limoniae essence 1g
Chocolate essence 1g
Magnesium stearate 10g
Two. preparation method
In the prescription ratio take by weighing stearic acid, be heated to 70 ~ 80 ℃, be fused into liquid (
).
2. the ratio in prescription takes by weighing respectively CEFUROXIME AXETIL, cross-linked carboxymethyl cellulose sodium (A), sodium lauryl sulphate, micropowder silica gel mix homogeneously; add in the turbine granulator, open turbine granulator, the control inlet temperature makes the material boiling; temperature remains on 25 ~ 30 ℃, will (
) slowly be sprayed onto on the material by aerodynamic atomization, sprayed rear discharging, sieve, get midbody particle (
).
In the prescription ratio take by weighing polyethylene glycol 6000, be heated to 70 ~ 75 ℃, be fused into liquid (
).
In the ratio of prescription take by weighing cross-linked carboxymethyl cellulose sodium (B), sucrose, xanthan gum, guar gum and (
) mix homogeneously, add in the turbine granulator, open turbine granulator, the control inlet temperature makes temperature of charge remain on 20 ~ 30 ℃, will (
) slowly be sprayed onto on the material by aerodynamic atomization, sprayed rear discharging, get cefuroxime axetil granule (
).
In the ratio of prescription take by weighing magnesium stearate, Fructus Citri Limoniae essence, chocolate essence and (
) mix homogeneously, packing gets cefuroxime axetil for suspension.
Three. as a result relative analysis
CEFUROXIME AXETIL is a kind of medicine with strong bitterness, need when preparing its granule and dry suspension its parcel is covered its bitterness, because CEFUROXIME AXETIL is all unstable to water and heat, form jelly during with the medium contact such as water, adopt the granule of wet method preparation hard, the risk that forms gel is arranged in vivo, reduce bioavailability.CN1054508C discloses a kind of preparation method of cefuroxime axetil granule, the method is traditional melt granulation, CEFUROXIME AXETIL is dispersed in the stearic acid and Palmic acid mixture of the melting more than 3 times (70 ℃), the medicine heated times such as CEFUROXIME AXETIL length easily causes its decomposition, and the low melting point consumption is large, affect its stripping in vivo, its bioavailability of listing product that adopts its technology to make only is 80% of tablet, and mouthfeel neither be ideal.The present invention prepares the method for cefuroxime axetil for suspension, only need the low melting point with material equivalent to be granulated, and medicine is under the lower temperature (20 ~ 30 ℃) all the time, the decomposition of having avoided the temperature height to cause, and the granule that makes is tiny evenly, good fluidity, when oral without grittiness, and agreeable to the taste fragrant and sweet flavor is arranged, and mouthfeel is good.
Example 5: roxithromycin capsules
One.Prescription (1000 meters)
Roxithromycin 165g
Carboxymethylstach sodium (A) 30g
Polyethylene glycol 6000 15g
Two. preparation method
In the prescription ratio take by weighing polyethylene glycol 6000, be heated to 95 ~ 100 ℃, be fused into liquid (
).
2. the ratio in prescription takes by weighing respectively Roxithromycin, carboxymethylstach sodium (A) mix homogeneously, adds in the fluid bed granulator, opens fluid bed granulator, and the control inlet temperature makes the material boiling, and temperature remains on 30 ~ 45 ℃, will (
) slowly be sprayed onto on the material by aerodynamic atomization, sprayed rear discharging, sieve, get midbody particle (
), divide encapsulated.
Three. as a result relative analysis
Water viscosity is very large because Roxithromycin is met, and the grain that makes during wet granulation is hard, affects the dissolution of medicine, and at present domestic all is direct packaging capsule after adopting the Roxithromycin raw material to mix with adjuvant, but because poor fluidity causes content uniformity large; Even by the Roxithromycin that the present invention makes, good fluidity, loading amount is stable during filled capsules, and capsule dissolubility is all more than 90%.
Example 6: the clarithromycin granule agent
One. prescription (1000 bags of meters)
Clarithromycin 100g
Carboxymethylstach sodium (A) 6g
Stearic acid 30g
Glyceryl Behenate 20g
Carboxymethylstach sodium (B) 30g
Sucrose 700g
Polyethylene glycol 6000 100g
Aspartame 5g
Fructus Citri Limoniae essence 1g
Chocolate essence 1g
Two. preparation method
1. the ratio in prescription takes by weighing stearic acid, Glyceryl Behenate, mixes, and is heated to 70 ~ 80 ℃, be fused into liquid (
).
2. the ratio in prescription takes by weighing respectively CEFUROXIME AXETIL, carboxymethylstach sodium (A) mix homogeneously, add in the turbine granulator, and open turbine granulator, the control inlet temperature makes the material boiling, and temperature remains on 25 ~ 45 ℃, will (
) slowly be sprayed onto on the material by aerodynamic atomization, sprayed rear discharging, sieve, get midbody particle (
).
In the prescription ratio take by weighing polyethylene glycol 6000, be heated to 70 ~ 75 ℃, be fused into liquid (
).
In the ratio of prescription take by weighing carboxymethylstach sodium (B), sucrose, aspartame and (
), Fructus Citri Limoniae essence, chocolate essence mix homogeneously, add in the turbine granulator, open turbine granulator, the control inlet temperature makes temperature of charge remain on 25 ~ 40 ℃, will (
) slowly be sprayed onto on the material by aerodynamic atomization, sprayed rear discharging, get clarithromycin granule, packing gets the clarithromycin granule agent.
Three. as a result relative analysis
The clarithromycin bitter in the mouth need adopt parcel taste masking technology to cover its bitterness when preparing its granule, dry suspension, dry syrup.CN1960716B discloses the manufacture method of the preparations such as clarithromycin dry syrup, and the method is traditional melt granulation, clarithromycin is dispersed in the glyceryl monostearate of its 2 times of meltings more than the amount (120 ℃).Temperature is high in this method manufacture process, the medicine heated times such as clarithromycin are long easily to cause its decomposition, and the low melting point consumption is large, affects its stripping in vivo, and need to add Eudragit E100 and help its release, and mouthfeel neither be ideal.The present invention prepares the method for agent, low melting point that only need 0.5 times of amount of material be granulated, and medicine is under the lower temperature (25 ~ 45 ℃) all the time, the decomposition of having avoided the temperature height to cause, and stearic acid dosage can be dissolved in intestinal juice less and made drug release, do not need to add Eudragit E100 and help its release, and the granule that makes is tiny evenly, good fluidity, when oral without grittiness, and agreeable to the taste fragrant and sweet flavor is arranged, and mouthfeel is good.
Example 7: cefuroxime axetil tablets
One. prescription (1000 meters)
CEFUROXIME AXETIL 300g
Microcrystalline Cellulose 60g
Micropowder silica gel 5g
Cross-linked carboxymethyl cellulose sodium 60g
Carboxymethylstach sodium 10g
Sodium lauryl sulphate 0.4g
Polyoxyethylene stearate (40) ester 20g
Polyethylene glycol 6000 50g
Stearic acid 2g
Two. preparation method
In the prescription ratio take by weighing polyoxyethylene stearate (40) ester, polyethylene glycol 6000, be heated to 70 ~ 75 ℃, be fused into liquid (
).
2. the ratio in prescription takes by weighing respectively CEFUROXIME AXETIL, microcrystalline Cellulose, micropowder silica gel, cross-linked carboxymethyl cellulose sodium, sodium lauryl sulphate, carboxymethylstach sodium mix homogeneously; add in the turbine granulator; open turbine granulator; the control inlet temperature makes the material boiling; temperature remains on 25 ~ 30 ℃, will (
) slowly be sprayed onto on the material by aerodynamic atomization, sprayed rear discharging, granulate, get cefuroxime axetil granule (
).
In the prescription ratio take by weighing stearic acid with (
) mix homogeneously, tabletting, then technique is bundled into Film coated tablets routinely.
Three. as a result relative analysis
Because CEFUROXIME AXETIL is amorphous powder, mobile non-constant can not direct compression, must granulate first and improve its flowability, because CEFUROXIME AXETIL is all unstable to water and heat, form jelly during with the medium contact such as water, can not adopt wet granulation, dry granulation is all adopted at present production, but dry granulation makes the granule irregularity, needs repeated multiple times dry-pressing granulation and material all in one piece, although mobile being improved, but still be not ideal, and production efficiency is low.The granule that preparation method of the present invention makes is tiny evenly, good fluidity, and production efficiency is high.
Example 8: Ceruroxime axetil capsules
One. prescription (1000 meters)
CEFUROXIME AXETIL 150g
Micropowder silica gel 2g
Cross-linked carboxymethyl cellulose sodium 30g
Carboxymethylstach sodium 5g
Sodium lauryl sulphate 0.2g
Polyoxyethylene stearate (40) ester 5g
Polyethylene glycol 6000 20g
Stearic acid 2g
Two. preparation method
In the prescription ratio take by weighing polyoxyethylene stearate (40) ester, polyethylene glycol 6000, be heated to 70 ~ 75 ℃, be fused into liquid (
).
2. the ratio in prescription takes by weighing respectively CEFUROXIME AXETIL, micropowder silica gel, cross-linked carboxymethyl cellulose sodium, sodium lauryl sulphate, carboxymethylstach sodium mix homogeneously; add in the turbine granulator, open turbine granulator, the control inlet temperature makes the material boiling; temperature remains on 25 ~ 30 ℃, will (
) slowly be sprayed onto on the material by aerodynamic atomization, sprayed rear discharging, granulate, get cefuroxime axetil granule (
).
In the prescription ratio take by weighing stearic acid with (
) mix homogeneously, divide encapsulated.
Three. as a result relative analysis
Because CEFUROXIME AXETIL is amorphous powder, mobile non-constant can not the direct packaging capsule, must granulate first and improve its flowability, because CEFUROXIME AXETIL is all unstable to water and heat, form jelly during with the medium contact such as water, can not adopt wet granulation, dry granulation is all adopted at present production, but dry granulation makes the granule irregularity, needs repeated multiple times dry-pressing granulation and material all in one piece, although mobile being improved, but still be not ideal, and production efficiency is low.The granule that preparation method of the present invention makes is tiny evenly, good fluidity, and production efficiency is high.
Example 9: Cefdinir dry suspension agent
One. prescription (1000 bags of meters)
Cefdinir 100g
Cross-linked carboxymethyl cellulose sodium 8g
Sodium lauryl sulphate 1g
Micropowder silica gel 1g
Sucrose 1750g
Citric acid 0.2g
Sodium citrate 0.4g
Polyoxyethylene stearate (40) ester 40g
Polyethylene glycol 6000 80g
Fructus Citri Limoniae essence 1g
Chocolate essence 1g
Magnesium stearate 10g
Two. preparation method
1. the ratio in prescription takes by weighing polyoxyethylene stearate (40) ester, polyethylene glycol 6000, mixes, and is heated to 70 ~ 75 ℃, be fused into liquid (
).
2. the ratio in prescription takes by weighing respectively cefdinir, cross-linked carboxymethyl cellulose sodium, sodium lauryl sulphate, micropowder silica gel, sucrose, citric acid, sodium citrate mix homogeneously; add in the turbine granulator; open turbine granulator; the control inlet temperature makes the material boiling; temperature remains on 25 ~ 30 ℃, will (
) slowly be sprayed onto on the material by aerodynamic atomization, sprayed rear discharging, sieve, get midbody particle (
).
In the ratio of prescription take by weighing magnesium stearate, Fructus Citri Limoniae essence, chocolate essence and (
) mix homogeneously, packing gets cefuroxime axetil for suspension.
Three. as a result relative analysis
Cefdinir belongs to-lactam antibiotics, all unstable to water and heat, at present the method for granulating of the disclosed cefdinir preparation of document is to adopt water and ethanol as the wet granulation method of wetting agent, need in the manufacture process water, ethanol volatilized under higher temperature and remove, not only energy consumption is high, and can cause environmental pollution, and in drying course because temperature is higher, affect the stability of cefdinir.The present invention prepares the method for Cefdinir dry suspension agent, and medicine is under the lower temperature (25 ~ 30 ℃) all the time, the decomposition of cefdinir when having avoided temperature higher, improved the stability of product, and do not used solvent, energy consumption is low, there is not pollutant emission, environmental protection.
Claims (8)
1. the method for granulating of a new oral solid preparation; it is characterized in that adopting fluid bed granulator or turbine granulator; the fused solution atomizing of low melting point is sprayed on the medicine and the acceptable adjuvant mixed material of pharmacy of boiling; regulating inlet temperature remains on below the low melting point freezing point material; and be no more than 45 ℃, low melting point solidifies material is bonded into granule.
2. low melting point according to claim 1, its fusing point is between 35 ~ 90 ℃.
3. low melting point according to claim 2, its fusing point is between 40 ~ 80 ℃.
4. low melting point according to claim 1 includes but not limited in Polyethylene Glycol, polyoxyl stearate, the stearic acid, behenic acid glyceride etc. one or more.
5. low melting point according to claim 1, the mass ratio of itself and mixed material to be granulated at 1:25 between the 1:1.
6. described method of granulating is used for the granulation of oral drugs solid preparation according to claim 1.
7. described method of granulating is suitable to heat and/or to granulation wet and/or unstable to solvent and/or that have polymorphic and/or need wrap up by granulating the medicine that improve the preparation mouthfeel according to claim 6.
According to claim 6 or 7 described medicines include but not limited to candesartan Cilexetil and compound preparation thereof ,-lactam drugs, Macrocyclolactone lactone kind medicine etc.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104586803A (en) * | 2015-02-12 | 2015-05-06 | 浙江华海药业股份有限公司 | Preparation method of empagliflozin microcrystalline cellulose composition |
| CN106539791A (en) * | 2016-10-19 | 2017-03-29 | 上海信谊万象药业股份有限公司 | A kind of valsartan amlodipine piece and preparation method thereof |
| WO2022151994A1 (en) * | 2021-01-18 | 2022-07-21 | 广州一品红制药有限公司 | Amlodipine dry suspension and preparation method therefor |
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| CN104586803A (en) * | 2015-02-12 | 2015-05-06 | 浙江华海药业股份有限公司 | Preparation method of empagliflozin microcrystalline cellulose composition |
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| WO2022151994A1 (en) * | 2021-01-18 | 2022-07-21 | 广州一品红制药有限公司 | Amlodipine dry suspension and preparation method therefor |
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