CN101548953A - Medicine granule, preparation method thereof, and preparation containing same - Google Patents
Medicine granule, preparation method thereof, and preparation containing same Download PDFInfo
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- CN101548953A CN101548953A CNA2008100356627A CN200810035662A CN101548953A CN 101548953 A CN101548953 A CN 101548953A CN A2008100356627 A CNA2008100356627 A CN A2008100356627A CN 200810035662 A CN200810035662 A CN 200810035662A CN 101548953 A CN101548953 A CN 101548953A
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Abstract
The invention discloses a medicine granule containing the following components by mass percent: 75 to 95 of medicine, 2 to 22 of thinner for pelletization, 0.06t to 0.5 of glidant, and 1.5 to 3.5 of adhesive. The invention also discloses a preparation method thereof and a preparation containing same. The medicine granule has high medicine content, round surface, higher rigidity and smaller grain diameter, can be directly used for tabletting, has less weight increment if being coated and can achieve a better taste masking effect. The method for preparing the medicine granule can simultaneously realize pelletization and coating technologies in a tangent spraying fluidized bed, has simple production steps and high efficiency, and can be applied to mass production.
Description
Technical field
The present invention relates to a kind of drug microparticles and preparation method thereof and contain the preparation of this microgranule.
Background technology
Solid dosage formss such as dry suspension, fine grained agent and oral cavity disintegration tablet because unit volume is little or can be in the oral cavity disintegrate rapidly, be particularly suitable for old man, child and other have the patient of dysphagia.Above-mentioned dosage form is made by drug microparticles usually.The contained medicament contg of existing drug microparticles is lower, can not satisfy the preparation requirement of the bigger medicine of dosage.Have the medicine of poor taste more greatly and simultaneously for dosage, this problem is even more serious, only relies on to add the good filler of mouthfeel and correctives deficiency so that bitterness is covered in the oral cavity.Coating is a method in common coating.Coating be divided into powder coating and with the prefabricated grain coating.For states of matter be Powdered, easily produce the medicine of static, mobile difference if directly powder coating is then to the requirement height of equipment, and because the crude drug crystal structure is hard and crisp, be easy to fragmentation, itself there are not plasticity and elasticity, need to use a large amount of auxiliary agents, this active component to high load capacity is infeasible, and the coating weightening finish will be bigger; In the prefabricated grain coating, after most of bibliographical information adopts the manual wet granulation of elder generation, adopt end spray or top spray fluid bed to carry out coating again, the drug microparticles hole of this method preparation is big, rough surface, hardness are little, in coating, be difficult to resist certain mechanism, and not being suitable for large-scale production, efficient is lower.
In the preparation method of pseudo-that the quick oral cavity disintegration tablet of 200610049248.2 1 kinds of ammonia phenol of patent, adopt fluid bed to the medicine coating again of granulating earlier, but the content of the active component of flavor-hidden pharmaceutical microgranule for preparing in this technology and oral cavity disintegration tablet is low, is lower than 35%; And the taste masking diameter of particle of preparation is big, is 450 μ m, and particle diameter produces grittiness than Da Yi in mouth, and easily broken during tabletting.
The mouthfeel of oral cavity disintegration tablet is to need a key factor considering in the preparation of said preparation.Therefore, the flavor-hidden pharmaceutical microgranule that is used to prepare oral cavity disintegration tablet need have better hardness, makes it can be because of broken and not discharge bitterness under bigger tabletting pressure effect.If drug microparticles intensity is too little, not crisp broken for guaranteeing it, need to adopt less tabletting pressure, but this can cause again oral cavity disintegration tablet to be difficult to be shaped, and perhaps dose more filler, and this will cause drug loading low.
With the flavor-hidden pharmaceutical microgranule suspension problem that to prepare a major issue that dry suspension need solve be the flavor-hidden pharmaceutical microgranule.The easy sedimentation of granule meeting that particle diameter is big, the suspension of granule itself is poor, needs to add more suspending agent, and this will cause, and cost increases, drug loading reduces.
Summary of the invention
Technical problem to be solved by this invention be for the content that overcomes existing drug microparticles low, it is big not to be suitable for dosage, especially simultaneously the defective of preparation that has the pharmaceutical preparation of poor taste, and provide a kind of have higher medicament contg, stronger hardness and the drug microparticles that can have taste masking effect preferably and smaller particle size, and contain the pharmaceutical preparation of this microgranule and their preparation method.
Drug microparticles of the present invention contains: 75～95% medicine, 2～22% diluent, 0.06～0.5% fluidizer and 1.5～3.5% binding agent; Percentage ratio is mass percent.
Wherein, described medicine can be the bigger medicine of dosage, as acetaminophen, aspirin, ibuprofen, cimetidine, diclofenac sodium or ranitidine.
Wherein, described diluent can be this area diluent commonly used, one or more in preferred lactose, starch and the microcrystalline Cellulose.
Wherein, fluidizer can be this area fluidizer commonly used, one or more in preferred micropowder silica gel, Pulvis Talci and the magnesium stearate.This composition has multiple function, and as lubricant, porosity depressant, grain density dose or moisture trapping agent, but major function is the flow aid as medicine.
Wherein, described binding agent can be this area typical binders, preferred hydroxypropyl methylcellulose and/or polyvinylpyrrolidone.Wherein, the preferable selection viscosity of hydroxypropyl methylcellulose is the specification of 5cPs or 50cPs, selection PVP K30 that polyvinylpyrrolidone is preferable or K29/32 (being that mean molecule quantity is 30000 or 29000/32000).The viscosity of these two kinds of preferred adhesive is lower, and spreading coefficient is little.Preparation is during drug microparticles, with the binding agent water be mixed with concentration preferable be that the binder aqueous solution of 2～8g/100ml uses.
Surface at the said medicine microgranule coats one deck coating again, is the drug microparticles with taste masking effect.The content of described coating accounts for 5～20% of whole drug microparticles quality; Described coating contains 54～85% coating material, 5～35% antiplastering aid and 10～21% plasticizer; Percentage ratio is mass percent.
Wherein, described coating material can be this area coating material commonly used, preferable be selected from ethyl cellulose, full water ethylcellulose dispersion and the acrylic resin one or more, preferred commercial goods is ethyl cellulose (can be buied by the auspicious safe chemical industry company limited in Shandong), homemade IV acrylic resin (can be buied by Lianyun Harbour company of rising of unit), full water ethylcellulose dispersion (can block happy Kanggong department by the U.S. buys), acrylic resin
EPO, acrylic resin
L30D, acrylic resin
NE30D and acrylic resin
FS30D (acrylic resin
Series of products can be buied by goldschmidt chemical corporation).Better preferred coating material is the blend of ethyl cellulose and homemade IV acrylic resin, and wherein, what the mass ratio of ethyl cellulose and homemade IV acrylic resin was preferable is 1: 1～1: 8, and better is 1: 3～1: 4; Perhaps full water ethylcellulose dispersion and acrylic resin
The blend of EPO, wherein, complete contained solid masses and the acrylic resin of water ethylcellulose dispersion
What the mass ratio of EPO was preferable is 1: 1～1: 8, and better is 1: 3～1: 4.Use acrylic resin
EPO is during as coating material, and is preferable when the preparation coating solution, also adds sodium lauryl sulphate as surfactant, and consumption can be acrylic resin
10% of EPO quality.
Wherein, described antiplastering aid can be this area antiplastering aid commonly used, preferably talc powder and/or glyceryl monostearate.
Wherein, described plasticizer can be this area common plasticizers, one or more in preferably glycerine, dibutyl phthalate, diethyl phthalate, stearic acid, Polyethylene Glycol, triethyl citrate and the triacetyl glycerine.
That the particle diameter of drug microparticles of the present invention is preferable is 60～250 μ m, and that better is 90～180 μ m; What the angle of repose of drug microparticles was preferable is 28～38 °; (assay method can be with reference to " pharmaceutics " the 5th edition by measuring bulk density and tap density, the People's Health Publisher, chief editor Cui Fude), obtain the degree of compression of drug microparticles preferable be 5～15%, better is 7～15% (degrees of compression=(tap density-bulk density)/tap density * 100%); Adopt air-flow to blow the friability that method is measured drug microparticles, that friability is preferable is 1～10% (but assay method list of references: Tang Xing, " research of theophylline albuterol compound multi-component delivery system one slow-release micro-pill ", Shenyang Pharmaceutical University's doctorate paper calendar year 2001); Under the same conditions, the tensile strength of the tablet of being made by drug microparticles of the present invention is higher than the tensile strength of the tablet of being made by medicine material medicine of the same race.
The invention still further relates to the preparation method of drug microparticles of the present invention, comprise the steps:
Medicine material powder, diluent, fluidizer are mixed with high shear process by doubly mensuration, place tangent line spray fluid bed, make its fluidisation and be heated to 24～35 ℃; The aqueous solution of binding agent is sprayed onto on the dry blend thing of medicine material powder, diluent and fluidizer by atomizing lance, makes it form drug microparticles, drying can make drug microparticles of the present invention.That wherein, the concentration of binder aqueous solution is preferable is 2～8g/100ml.
What the operating condition of the tangent line spray fluid bed of above-mentioned granulating process was preferable is: the blower fan frequency is 15～30Hz; Inlet temperature is 30～40 ℃; Temperature of charge is 24～35 ℃; The rotational frequency of rotating disk is 120～500rpm; The atomizing pressure of atomizing lance is 0.05～0.25MPa; Hydrojet speed is 3～6g/min.
In order to prepare the drug microparticles that outer surface covers coating with taste masking effect, behind above-mentioned drying steps, then make the drug microparticles fluidisation and be heated to 35～55 ℃, coating material, antiplastering aid and plasticizer are dispersed in water or the ethanol water, the coating solution that forms is sprayed onto on the microgranule by atomizing lance, to increasing weight 5～25%, dry aging, the drug microparticles that can obtain having the taste masking effect.Wherein, what the concentration of ethanol water was preferable is mass percent 65～95%, the concentration of coating solution preferable for the total content of coating material, antiplastering aid and plasticizer be mass percent 8～15%.
What the operating condition of the tangent line spray fluid bed of above-mentioned art for coating was preferable is: the blower fan frequency is 15～30Hz; Inlet temperature is 40～60 ℃; Temperature of charge is 35～55 ℃; The rotational frequency of rotating disk is 100～200rpm; The atomizing pressure of atomizing lance is 0.05～0.25MPa; The hydrojet speed of coating solution is 2～6g/min.
Above-mentioned preferred process conditions can make drug microparticles of the present invention have smaller particle size, and stronger hardness and crushing resistance, and smooth surface, rounding are beneficial to effective reduction coating weightening finish, satisfy the requirement at preparations such as preparation oral disintegrating tablet formulation and dry suspension.Wherein, preferred atomizing pressure can make binding agent and coating solution keep less drop size; Preferred rotary speed can guarantee to have enough centrifugal to active force.
The present invention also further relates to the pharmaceutical preparation that contains drug microparticles of the present invention, comprises oral cavity disintegration tablet, dry suspension or granule etc.What described pharmaceutical preparation was preferable is oral cavity disintegration tablet and dry suspension.
Among the present invention, the better formula of described oral cavity disintegration tablet is: contain 31～70% drug microparticles, 21%～60% tablet diluent, 2～8% disintegrating agent and 0.5～1% lubricant.
Wherein, described tablet diluent can be this area convas tablet diluent, in preferably microcrystalline cellulose, lactose, sorbitol and the mannitol one or more, the more preferably self-control tablet diluent that makes by following method: lactose and the microcrystalline Cellulose mass ratio with 2: 1～5: 1 is mixed, place tangent line spray fluid bed, make its fluidisation and be heated to 24～35 ℃; The aqueous solution of binding agent is sprayed onto on the dry blend thing of lactose and microcrystalline Cellulose by atomizing lance, makes it form granule, when granule grows to 60～250 μ m, dry get final product, specifically the fluidized bed process step of fluidized bed process step such as above-mentioned granulating process.Wherein, binding agent can be this area typical binders, and preferred reagent as previously mentioned.That wherein, the concentration of binder aqueous solution is preferable is 2～8g/100ml.
Wherein, disintegrating agent can be this area convas tablet disintegrating agent, one or more in preferred polyvinylpolypyrrolidone, sodium carboxymethyl cellulose and the crosslinked carboxymethyl fecula sodium.
Wherein, lubricant can be this area conventional lubricants, preferred magnesium stearate.
The preparation method of described oral cavity disintegration tablet can be: drug microparticles, tablet diluent and disintegrating agent by doubly mensuration mixing, are added lubricant, then tabletting before compacting.
Oral cavity disintegration tablet contained drug active component content height of the present invention, and uniformity of dosage units is better, need not to use water delivery service, disintegrate in 5～90s in the oral cavity, no bitterness, no grittiness.
Among the present invention, the better formula of described dry suspension is: contain 50～65% drug microparticles, 33～48% suspending agents and 1～2% essence.
Wherein, described suspending agent can be this area suspending agent commonly used, one or more in preferably microcrystalline cellulose, sodium carboxymethyl cellulose and the hydroxypropyl methylcellulose, more preferably the self-control suspending agent that makes according to following direct powder coating method or granule coating method:
Direct powder coating method: microcrystalline Cellulose is placed tangent line spray fluid bed, make its fluidisation and be heated to 35～55 ℃, the aqueous solution of sodium carboxymethyl cellulose is sprayed onto on the microcrystalline Cellulose fluidized bed process step of concrete fluidized bed process step such as above-mentioned granulating process with atomizing lance;
The granule coating method: microcrystalline Cellulose is placed tangent line spray fluid bed, and fluidisation also is heated to 24～35 ℃, and the aqueous solution of binding agent is sprayed onto on the microcrystalline Cellulose, make the formation granule, grow to 60～150 μ m, drying, the fluidized bed process step of concrete fluidized bed process step such as above-mentioned granulating process; With grain fluidized and be heated to 35～55 ℃, the spraying of the aqueous solution of reuse sodium carboxymethyl cellulose makes granule grow to 80～250 μ m, drying, the fluidized bed process step of concrete fluidized bed process step such as above-mentioned art for coating.
Wherein, described essence can be this area essence commonly used, as flavoring orange essence, Fructus Citri Limoniae essence or vanilla.
The preparation method of described dry suspension can be: taste masking microgranule and suspending agent are fully mixed, spray into essence promptly.
The present invention is raw materials used and reagent is all commercially available gets.Among the present invention, described percentage ratio is mass percent.
Positive progressive effect of the present invention is:
(1) drug microparticles Chinese medicine content height of the present invention, surperficial rounding can have smaller particle size and stronger hardness, can be directly used in tabletting, if carry out coating, it is less to increase weight, and can reach taste masking effect preferably.
(2) because drug microparticles particle diameter of the present invention is little, and intensity is stronger, and the coating material of excellent usefulness has certain toughness, adopt its preparation during oral cavity disintegration tablet, can be in less pressure lower sheeting molding, and taste masking is effective.If select the self-control tablet diluent for use, then effect is better.
(3) drug microparticles particle diameter of the present invention is less, suspension good, when adopting its preparation dry suspension, guarantees the suspended state of drug microparticles.If select the self-control suspending agent for use, then effect is better.
(4) the present invention prepares the method for drug microparticles, can spray at tangent line to realize simultaneously in the fluid bed granulating and art for coating, and production stage is simple, and efficient is higher, can be applicable to large-scale production.
The specific embodiment
Mode below by embodiment further specifies the present invention, but does not therefore limit the present invention among the described scope of embodiments.
Embodiment 1
Acetaminophen 300g (75%), lactose 88g (22%) and micropowder silica gel 2g (0.5%) are mixed with high shear process by doubly mensuration, place tangent line spray fluid bed, adopt blower fan frequency 27Hz, 30 ℃ of inlet temperature, atomizing pressure 0.25MPa, rotary speed 500rpm, hydrojet speed 4g/min, material is heated to 24 ℃, 4g/100ml hydroxypropyl methylcellulose (viscosity is 5cPs) aqueous solution (containing hydroxypropyl methylcellulose 10g (2.5%)) is sprayed onto on the dry blend thing of heating, make the formation drug microparticles, it is dry to heat up, and promptly gets the acetaminophen drug microparticles.The acetaminophen medicament contg is 75%, and diameter of particle is 80～180 μ m, 28 ° of angle of reposes, and the degree of compression 8%, the tablet that friability 1.4%, microgranule are made is than the tablet tensile strength height made from crude drug under the condition.
Connect aforementioned preparation process, in tangent line spray fluid bed, adopt blower fan frequency 18Hz, 40 ℃ of inlet temperature, atomizing pressure 0.2MPa, rotary speed 150rpm, hydrojet speed 2g/min, drug microparticles are heated to 35 ℃, will
EPO 40g (accounting for coating 65%), sodium lauryl sulphate 4g (accounting for coating 6.5%), stearic acid 6.15g (accounting for coating 10%), Pulvis Talci 11.4g (accounting for coating 18.5%) are dispersed in the coating solution (mass fraction of solids is 20%) that forms in the water and are sprayed onto on the drug microparticles, 5.3% stop to increasing weight, dry aging, the acetaminophen drug microparticles that promptly obtains having the taste masking effect.Coating accounts for microgranule total amount 5%; Diameter of particle is 100～180 μ m; 28 ° of angle of reposes; The degree of compression 5%; Friability 1%; Has tablet that this microgranule of taste masking effect makes than with crude drug under the condition and the tablet tensile strength height made of the drug microparticles of coating not.
Above-mentioned drug microparticles 77.5 (31%), spray-dried lactose 110g (44%), mannitol 40g (16%), polyvinylpolypyrrolidone 20g (8%) and magnesium stearate 2.5g (1%) with taste masking effect mixed, make 1000, every 0.25g.The oral cavity disintegration tablet that makes is the 30s disintegrate in mouth, no grittiness, no bitterness.The external stripping of acetaminophen (oar method) 40min stripping 92.7%.
Above-mentioned drug microparticles 90g (50%) and self-control suspending agent 86.4g (48%) with taste masking effect mixed, spray into 3.6g flavoring orange essence (2%), make 300 bags of dry suspension, every bag of 600mg.
Wherein the self-control suspending agent in the dry suspension is made by direct powder coating method: microcrystalline Cellulose is placed tangent line spray fluid bed, adopt blower fan frequency 15Hz, 40 ℃ of inlet temperature, atomizing pressure 0.2MPa, rotary speed 120rpm, hydrojet speed 3g/min, microgranule is heated to 35 ℃, the aqueous solution (1g/100ml) of sodium carboxymethyl cellulose is sprayed onto on the microcrystalline Cellulose with atomizing lance, gets final product.
Embodiment 2
Ranitidine 380g (95%), starch 8g (2%) and Pulvis Talci 0.24g (0.06%) are mixed with high shear process by doubly mensuration, place tangent line spray fluid bed, adopt blower fan frequency 15Hz, 35 ℃ of inlet temperature, atomizing pressure 0.15MPa, rotary speed 300rpm, hydrojet speed 6g/min, material is heated to 30 ℃, 3g/100ml hydroxypropyl methylcellulose (viscosity is 50cPs) aqueous solution (containing hydroxypropyl methylcellulose 11.76g (2.94%)) is sprayed onto on the dry blend thing of heating, make the formation drug microparticles, it is dry to heat up, and promptly gets the ranitidine drug microparticles.The ranitidine medicament contg is 95%, and particle diameter is 60～240 μ m, 38 ° of angle of reposes, and the degree of compression 15%, the tablet that friability 10%, microgranule are made is than the tablet tensile strength height made from crude drug under the condition.
Connect aforementioned preparation process, in tangent line spray fluid bed, adopt blower fan frequency 15Hz, 60 ℃ of inlet temperature, atomizing pressure 0.05MPa, rotary speed 200rpm, hydrojet speed 3g/min, drug microparticles are heated to 55 ℃, will
NE30D 180g (contained solid masses accounts for coating 85%), triethyl citrate 7g (accounting for coating 10%) and glyceryl monostearate 3.5g (accounting for coating 5%) are dispersed in the coating solution (mass fraction of solids is 20%) that forms in the water and are sprayed onto on the drug microparticles, 15% stop to increasing weight, dry aging, the ranitidine drug microparticles that promptly obtains having the taste masking effect.Coating accounts for microgranule total amount 13%, and particle diameter is 100～250 μ m; 35 ° of angle of reposes, the degree of compression 14%, friability 2% has tablet that this microgranule of taste masking effect makes than with crude drug under the condition and the tablet tensile strength height made of the drug microparticles of coating not.
Above-mentioned drug microparticles 175g (70%), microcrystalline Cellulose 37.5g (15%), mannitol 15g (6%), polyvinylpolypyrrolidone 20g (8%) and magnesium stearate 2.5g (1%) with taste masking effect mixed, make 1000, every 0.25g.The oral cavity disintegration tablet that makes is the 40s disintegrate in mouth, no grittiness, no bitterness.To the external stripping of ranitidine (oar method) 40min stripping 95%.
Above-mentioned drug microparticles 117g (65%) and microcrystalline Cellulose 59.4g (33%) with taste masking effect mixed, spray into 3.6g flavoring orange essence (2%), make 300 bags of dry suspension, every bag of 600mg.
Embodiment 3
Aspirin 340g (85%), microcrystalline Cellulose 53g (13.25%) and magnesium stearate 1g (0.25%) are mixed with high shear process by doubly mensuration, place tangent line spray fluid bed, adopt blower fan frequency 30Hz, 35 ℃ of inlet temperature, atomizing pressure 0.05MPa, rotary speed 120rpm, hydrojet speed 3g/min, material is heated to 30 ℃, 2g/100ml hydroxypropyl methylcellulose (viscosity is 5cPs) aqueous solution (containing hydroxypropyl methylcellulose 1.5%) is sprayed onto on the dry blend thing of heating, make the formation drug microparticles, it is dry to heat up; Promptly obtain the aspirin drug microparticles.Aspirin content is 85%, and particle diameter is 100～200 μ m, and be 35 ° angle of repose, the degree of compression 15%, and the tablet that friability 7%, microgranule are made is than the tablet tensile strength height made from crude drug under the condition.
Connect aforementioned preparation process, in tangent line spray fluid bed, adopt blower fan frequency 30Hz, 55 ℃ of inlet temperature, atomizing pressure 0.25MPa, rotary speed 100rpm, hydrojet speed 4g/min, drug microparticles is heated to 50 ℃, with ethyl cellulose 7g (accounting for coating 6%), homemade IV acrylic resin 56g (accounting for coating 48%), diethyl phthalate 12.8g (accounting for coating 11%), Pulvis Talci 40.8g (accounting for coating 35%) is dispersed in the coating solution (mass fraction of solids is 15%) that forms in 85% ethanol (mass percent) and is sprayed onto on the drug microparticles, 18.5% stop to increasing weight, dry aging, the aspirin drug microparticles that promptly obtains having the taste masking effect.Coating accounts for microgranule total amount 15.6%, and particle diameter is 100～220 μ m, 32 ° of angle of reposes, and the degree of compression 13%, friability 5% has tablet that this microgranule of taste masking effect makes than with crude drug under the condition and the tablet tensile strength height made of the drug microparticles of coating not.
Above-mentioned drug microparticles 125g (50%), spray-dried lactose 70g (40%), mannitol 30g (7.5%), polyvinylpolypyrrolidone 18g (2%) and magnesium stearate 2g (0.5%) with taste masking effect mixed, make 1000, every 0.25g.The oral cavity disintegration tablet that makes is the 25s disintegrate in mouth, no grittiness, no bitterness.To the external stripping of aspirin (oar method) 40min stripping 90%.
Above-mentioned drug microparticles 108g (60%) and microcrystalline Cellulose 70.2 (39%) with taste masking effect mixed, spray into 1.8g flavoring orange essence (1%), make 300 bags of dry suspension, every bag of 600mg.
Embodiment 4
Cimetidine 324g (81%), lactose 60g (15%) and micropowder silica gel 2g (0.5%) are mixed with high shear process by doubly mensuration, place tangent line spray fluid bed, adopt blower fan frequency 20Hz, 36 ℃ of inlet temperature, atomizing pressure 0.1MPa, rotary speed 150rpm, hydrojet speed 5g/min, material is heated to 32 ℃, 8g/100ml PVP K29/32 aqueous solution (containing PVP K29/3214g (3.5%)) is sprayed onto on the dry blend thing of heating, make the formation drug microparticles, it is dry to heat up, and promptly gets the cimetidine drug microparticles.Cimetidine content is 82%, and particle diameter is 80～200 μ m, and be 30 ° angle of repose, the degree of compression 5%, and the tablet that friability 5%, microgranule are made is than the tablet tensile strength height made from crude drug under the condition.
Connect aforementioned preparation process, in tangent line spray fluid bed, adopt blower fan frequency 25Hz, 60 ℃ of inlet temperature, atomizing pressure 0.1MPa, rotary speed 100rpm, hydrojet speed 6g/min, drug microparticles is heated to 55 ℃, with full water ethylcellulose dispersion 31.58g (contained solid masses accounts for coating 6.58%),
EPO 62g (accounting for coating 52.64%), sodium lauryl sulphate 5.76g (accounting for coating 4.8%), dibutyl phthalate 25.2g (accounting for coating 21%), Pulvis Talci 18g (accounting for coating 15%) are dispersed in the coating solution (mass fraction of solids is 15%) that forms in the water and are sprayed onto on the drug microparticles, 10% stop to increasing weight, dry aging, the cimetidine drug microparticles that promptly obtains having the taste masking effect.Coating accounts for microgranule total amount 9.1%, and particle diameter is 90～220 μ m, 28 ° of angle of reposes, the degree of compression 5%, friability 2%, has tablet that this microgranule of taste masking effect makes than with crude drug under the condition and the tablet tensile strength height made of the drug microparticles of coating not.
Above-mentioned drug microparticles 87.5g (35%), self-control tablet diluent 107.5g (43%), sorbitol 37.5g (15%), crosslinked carboxymethyl fecula sodium 15.5g (6.2%) and magnesium stearate 2g (0.8%) with taste masking effect mixed, make 1000, every 0.25g.The oral cavity disintegration tablet that makes is the 25s disintegrate in mouth, no grittiness, no bitterness.The external stripping of cimetidine (oar method) 40min stripping 90%.
The self-control tablet diluent of wherein above-mentioned tablet diluent for making by following method: lactose and the microcrystalline Cellulose mass ratio with 2: 1 is mixed, place tangent line spray fluid bed, adopt blower fan frequency 30Hz, 40 ℃ of inlet temperature, atomizing pressure 0.1MPa, rotary speed 120rpm, hydrojet speed 6g/min, material is heated to 35 ℃, be sprayed onto 5g/100ml PVP K29/32 aqueous solution (containing PVP K29/3210g) on the dry blend thing of lactose and microcrystalline Cellulose by atomizing lance, make it form granule, when granule grows to 60～180 μ m, dry getting final product.
Above-mentioned drug microparticles 91g (50.5%) and hydroxypropyl methylcellulose 86.4g (48%) with taste masking effect mixed, spray into 2.6g flavoring orange essence (1.5%), make 300 bags of dry suspension, every bag of 600mg.
Embodiment 5
Ibuprofen 345.2g (86.3%), lactose 40g (10%) and micropowder silica gel 0.8g (0.2%) are mixed with high shear process by doubly mensuration, place tangent line spray fluid bed, adopt blower fan frequency 25Hz, 30 ℃ of inlet temperature, atomizing pressure 0.05MPa, rotary speed 400rpm, hydrojet speed 3g/min, material is heated to 24 ℃, 5g/100ml PVP K30 (PVP K3014g (3.5%)) solution is sprayed onto on the dry blend thing of heating, make the formation drug microparticles, it is dry to heat up, and promptly gets the ibuprofen pharmaceutical microgranule.Ibuprofen content is 86.3%, and particle diameter is 60～180 μ m, and be 30 ° angle of repose, the degree of compression 15%, and the tablet that friability 8%, microgranule are made is than the tablet tensile strength height made from crude drug under the condition.
Connect aforementioned preparation process, in tangent line spray fluid bed, adopt blower fan frequency 25Hz, 55 ℃ of inlet temperature, atomizing pressure 0.1MPa, rotary speed 100rpm, hydrojet speed 6g/min, drug microparticles are heated to 50 ℃, with full water ethylcellulose dispersion 32g (contained solid masses accounts for coating 18%),
EPO 24g (accounting for coating 54%), sodium lauryl sulphate 1.56g (accounting for coating 3.5%), triacetyl glycerine 6.89g (accounting for coating 15.5%), Pulvis Talci 4g (accounting for coating 9%) are dispersed in the coating solution (mass fraction of solids is 15%) that forms in the water and are sprayed onto on the drug microparticles, 15% stop to increasing weight, dry wearing out promptly obtains having the ibuprofen pharmaceutical microgranule of taste masking effect.Coating accounts for microgranule total amount 13%, and particle diameter is 60～190 μ m, 32 ° of angle of reposes, the degree of compression 8%, friability 5%, has tablet that this microgranule of taste masking effect makes than with crude drug under the condition and the tablet tensile strength height made of the drug microparticles of coating not.
Above-mentioned drug microparticles 106.2g (42.5%), self-control tablet diluent 112.5g (45%), mannitol 25g (10%), sodium carboxymethyl cellulose 5g (2%) and magnesium stearate 1.3g (0.5%) with taste masking effect mixed, make 1000, every 0.25g.The oral cavity disintegration tablet that makes is the 25s disintegrate in mouth, no grittiness, no bitterness.To the external stripping of ibuprofen (oar method) 40min stripping 90%.
The self-control tablet diluent of wherein above-mentioned tablet diluent for making by following method: lactose and the microcrystalline Cellulose mass ratio with 5: 1 is mixed, place tangent line spray fluid bed, adopt blower fan frequency 25Hz, 30 ℃ of inlet temperature, atomizing pressure 0.25MPa, rotary speed 500rpm, hydrojet speed 3g/min, material is heated to 24 ℃, be sprayed onto 8g/100ml PVP K30 (PVP K3014g) solution on the dry blend thing of lactose and microcrystalline Cellulose by atomizing lance, make it form granule, when granule grows to 80～180 μ m, dry getting final product.
Above-mentioned drug microparticles 135g (54%) and self-control suspending agent 112.5g (45%) with taste masking effect mixed, spray into 2.5g Fructus Citri Limoniae essence (1%), make 300 bags of dry suspension, every bag of 600mg.
Above-mentioned self-control suspending agent can be made by the granule coating method: microcrystalline Cellulose is placed tangent line spray fluid bed, adopt blower fan frequency 25Hz, 30 ℃ of inlet temperature, atomizing pressure 0.1MPa, rotary speed 500rpm, hydrojet speed 3g/min, material is heated to 24 ℃, and the aqueous solution (viscosity is 5cPs) of 1g/100ml hydroxypropyl methylcellulose is sprayed onto on the microcrystalline Cellulose, makes the formation microgranule, grow to 60～120 μ m, drying; Then adopt blower fan frequency 25Hz, 60 ℃ of inlet temperature, atomizing pressure 0.1MPa, rotary speed 100rpm, hydrojet speed 6g/min, microgranule is heated to 55 ℃, with aqueous solution (1g/100ml) spraying of sodium carboxymethyl cellulose, grow to 80～180 μ m, drying gets final product.
Embodiment 6
Diclofenac sodium 331.6g (82.9%), lactose 60g (15%) and micropowder silica gel 0.4g (0.1%) are mixed with high shear process by doubly mensuration, place tangent line spray fluid bed, adopt blower fan frequency 23Hz, 40 ℃ of inlet temperature, atomizing pressure 0.05MPa, rotary speed 300rpm, hydrojet speed 5g/min, material is heated to 35 ℃, 6g/100ml PVP K30 aqueous solution (PVP K308g (2%)) is sprayed onto on the dry blend thing of heating, make the formation drug microparticles, it is dry to heat up, and promptly gets the diclofenac sodium drug microparticles.The diclofenac sodium content is 82.9%, and particle diameter is 80～220 μ m, and be 38 ° angle of repose, the degree of compression 9%, and the tablet that friability 10%, microgranule are made is than the tablet tensile strength height made from crude drug under the condition.
Connect aforementioned preparation process, in tangent line spray fluid bed, adopt blower fan frequency 15Hz, 45 ℃ of inlet temperature, atomizing pressure 0.2MPa, rotary speed 100rpm, hydrojet speed 4g/min, drug microparticles is heated to 35 ℃, with ethyl cellulose 25g (accounting for coating 18.5%), homemade IV acrylic resin 74.3g (accounting for coating 55%), glycerol 20.3g (accounting for coating 15%), Pulvis Talci 15.5g (accounting for coating 11.5%) is dispersed in the coating solution (mass fraction of solids is 15%) that forms in 85% ethanol and is sprayed onto on the drug microparticles, 25% stop to increasing weight, dry aging, the diclofenac sodium drug microparticles that promptly obtains having the taste masking effect.Coating accounts for microgranule total amount 20%, and particle diameter is 100～220 μ m, 37 ° of angle of reposes, the degree of compression 7%, friability 10%, has tablet that this microgranule of taste masking effect makes than with crude drug under the condition and the tablet tensile strength height made of the drug microparticles of coating not.
Above-mentioned drug microparticles 125g (50%), spray-dried lactose 100g (40%), mannitol 12.5g (5%), hydroxypropyl methylcellulose 10g (4%) and magnesium stearate 2.5g (1%) with taste masking effect mixed, make 1000, every 0.25g.The oral cavity disintegration tablet that makes is the 25s disintegrate in mouth, no grittiness, no bitterness.The external stripping of diclofenac sodium (oar method) 40min stripping 90%.
Above-mentioned drug microparticles 92.2g (51.2%) and sodium carboxymethyl cellulose 86g (47.8%) with taste masking effect mixed, spray into 1.8g vanilla (1%), make 300 bags of dry suspension, every bag of 600mg.
Embodiment 7
Acetaminophen 345.2g (86.3%), lactose 40g (10%) and micropowder silica gel 0.8g (0.2%) are mixed with high shear process by doubly mensuration, place tangent line spray fluid bed, adopt blower fan frequency 20Hz, 30 ℃ of inlet temperature, atomizing pressure 0.05MPa, rotary speed 400rpm, hydrojet speed 3g/min, material is heated to 24 ℃, 7g/100ml PVP K30 (PVP K3014g (3.5%)) solution is sprayed onto on the dry blend thing of heating, make the formation drug microparticles, it is dry to heat up, and promptly gets the ibuprofen pharmaceutical microgranule.Acetaminophen content is 86.3%, and particle diameter is 60～180 μ m, and be 30 ° angle of repose, the degree of compression 10%, and the tablet that friability 8%, microgranule are made is than the tablet tensile strength height made from crude drug under the condition.
Connect aforementioned preparation process, in tangent line spray fluid bed, adopt blower fan frequency 25Hz, 55 ℃ of inlet temperature, atomizing pressure 0.1MPa, rotary speed 100rpm, hydrojet speed 6g/min, drug microparticles is heated to 50 ℃, with full water ethylcellulose dispersion 80g (contained solid masses accounts for coating 37.5%),
EPO 20g (accounting for coating 37.5%), sodium lauryl sulphate 1.87g (accounting for coating 3.5%), Polyethylene Glycol (mean molecule quantity 6000) 8g (accounting for coating 15%), glyceryl monostearate 3.46g (accounting for coating 6.5%) are dispersed in the coating solution (mass fraction of solids is 15%) that forms in the water and are sprayed onto on the drug microparticles, 8% stop to increasing weight, dry aging, the acetaminophen drug microparticles that promptly obtains having the taste masking effect.Coating accounts for microgranule total amount 7.4%, and particle diameter is 60～190 μ m, 32 ° of angle of reposes, the degree of compression 8%, friability 5%, has tablet that this microgranule of taste masking effect makes than with crude drug under the condition and the tablet tensile strength height made of the drug microparticles of coating not.
Above-mentioned drug microparticles 106.2g (42.5%), self-control tablet diluent 112.5g (45%), mannitol 25g (10%), sodium carboxymethyl cellulose 5g (2%) and magnesium stearate 1.3g (0.5%) with taste masking effect mixed, make 1000, every 0.25g.The oral cavity disintegration tablet that makes is the 25s disintegrate in mouth, no grittiness, no bitterness.The external stripping of acetaminophen (oar method) 40min stripping 90%.
The self-control tablet diluent of wherein above-mentioned tablet diluent for making by following method: lactose and the microcrystalline Cellulose mass ratio with 3: 1 is mixed, place tangent line spray fluid bed, adopt blower fan frequency 30Hz, 35 ℃ of inlet temperature, atomizing pressure 0.05MPa, rotary speed 400rpm, hydrojet speed 3g/min, material is heated to 30 ℃, be sprayed onto 7g/100ml PVP K30 (PVP K3014g) on the dry blend thing of lactose and microcrystalline Cellulose by atomizing lance, make it form granule, when granule grows to 80～250 μ m, dry getting final product.
Above-mentioned drug microparticles 135g (54%) and self-control suspending agent 112.5g (45%) with taste masking effect mixed, spray into 2.5g Fructus Citri Limoniae essence (1%), make 300 bags of dry suspension, every bag of 600mg.
Above-mentioned self-control suspending agent is made by the granule coating method: microcrystalline Cellulose is placed tangent line spray fluid bed, adopt blower fan frequency 30Hz, 40 ℃ of inlet temperature, atomizing pressure 0.05MPa, rotary speed 120rpm, hydrojet speed 6g/min, material is heated to 35 ℃, and 6g/100ml hydroxypropyl methylcellulose (50cPs) aqueous solution is sprayed onto on the microcrystalline Cellulose, makes the formation microgranule, grow to 80～150 μ m, drying; Then adopt blower fan frequency 25Hz, 40 ℃ of inlet temperature, atomizing pressure 0.05MPa, rotary speed 100rpm, hydrojet speed 6g/min, microgranule is heated to 35 ℃, with aqueous solution (5g/100ml) spraying of sodium carboxymethyl cellulose, grow to 100～250 μ m, drying gets final product.
Embodiment 8
Ranitidine 331.6g (82.9%), lactose 60g (15%) and micropowder silica gel 0.4g (0.1%) are mixed with high shear process by doubly mensuration, place tangent line spray fluid bed, adopt blower fan frequency 27Hz, 40 ℃ of inlet temperature, atomizing pressure 0.05MPa, rotary speed 300rpm, hydrojet speed 5g/min, material is heated to 35 ℃, 5g/100ml PVP K30 aqueous solution (PVP K308g (2%)) is sprayed onto on the dry blend thing of heating, make the formation drug microparticles, it is dry to heat up, and promptly gets the ranitidine drug microparticles.Ranitidine content is 82.9%, and particle diameter is 80～220 μ m, and be 38 ° angle of repose, the degree of compression 7%, and the tablet that friability 10%, microgranule are made is than the tablet tensile strength height made from crude drug under the condition.
Connect aforementioned preparation process, in tangent line spray fluid bed, adopt blower fan frequency 25Hz, 40 ℃ of inlet temperature, atomizing pressure 0.2MPa, rotary speed 100rpm, hydrojet speed 4g/min, drug microparticles is heated to 35 ℃, with ethyl cellulose 40g (accounting for coating 40%), homemade IV acrylic resin 40g (accounting for coating 40%), diethyl phthalate 10g (accounting for coating 10%), Pulvis Talci 10g (accounting for coating 10%) is dispersed in the coating solution (mass fraction of solids is 15%) that forms in 85% (mass percent) ethanol and is sprayed onto on the drug microparticles, 23% stop to increasing weight, dry aging, the ranitidine drug microparticles that promptly obtains having the taste masking effect.Coating accounts for microgranule total amount 18.7%, particle diameter is 100～220 μ m, 37 ° of angle of reposes, the degree of compression 5%, friability 10%, has tablet that this microgranule of taste masking effect makes than with crude drug under the condition and the tablet tensile strength height made of the drug microparticles of coating not.
Above-mentioned drug microparticles 125g (50%), spray-dried lactose 100g (40%), mannitol 12.5g (5%), hydroxypropyl methylcellulose 10g (4%) and magnesium stearate 2.5g (1%) with taste masking effect mixed, make 1000, every 0.25g.The oral cavity disintegration tablet that makes is the 25s disintegrate in mouth, no grittiness, no bitterness.To the external stripping of ranitidine (oar method) 40min stripping 90%.
Above-mentioned drug microparticles 104.4g (58%) and sodium carboxymethyl cellulose 72g (40%) with taste masking effect mixed, spray into 3.6g vanilla (2%), make 300 bags of dry suspension, every bag of 600mg.
Embodiment 9
Ranitidine 380g (95%), starch 8g (2%) and Pulvis Talci 0.24g (0.06%) are mixed with high shear process by doubly mensuration, place tangent line spray fluid bed, adopt blower fan frequency 30Hz, 35 ℃ of inlet temperature, atomizing pressure 0.15MPa, rotary speed 300rpm, hydrojet speed 6g/min, material is heated to 30 ℃, 3g/100ml hydroxypropyl methylcellulose (viscosity is 50cPs) aqueous solution (containing hydroxypropyl methylcellulose 11.76g (2.94%)) is sprayed onto on the dry blend thing of heating, make the formation drug microparticles, it is dry to heat up, and promptly gets the ranitidine drug microparticles.The ranitidine medicament contg is 95%, and particle diameter is 60～240 μ m, 38 ° of angle of reposes, and the degree of compression 10%, the tablet that friability 10%, microgranule are made is than the tablet tensile strength height made from crude drug under the condition.
Connect aforementioned preparation process, in tangent line spray fluid bed, adopt blower fan frequency 17Hz, 60 ℃ of inlet temperature, atomizing pressure 0.05MPa, rotary speed 200rpm, feed liquor speed 3g/min, drug microparticles are heated to 55 ℃, will
FS30D 180g (contained solid masses accounts for coating 85%), triethyl citrate 7g (accounting for coating 10%) and glyceryl monostearate 3.5g (accounting for coating 5%) are dispersed in the coating solution (mass fraction of solids is 20%) that forms in the water and are sprayed onto on the drug microparticles, 15% stop to increasing weight, dry aging, the ranitidine drug microparticles that promptly obtains having the taste masking effect.Coating accounts for microgranule total amount 13%, and particle diameter is 100～250 μ m; 35 ° of angle of reposes, the degree of compression 8%, friability 2% has tablet that this microgranule of taste masking effect makes than with crude drug under the condition and the tablet tensile strength height made of the drug microparticles of coating not.
Above-mentioned drug microparticles 175g (70%), microcrystalline Cellulose 37.5g (15%), mannitol 15g (6%), polyvinylpolypyrrolidone 20g (8%) and magnesium stearate 2.5g (1%) with taste masking effect mixed, make 1000, every 0.25g.The oral cavity disintegration tablet that makes is the 40s disintegrate in mouth, no grittiness, no bitterness.To the external stripping of ranitidine (oar method) 40min stripping 95%.
Above-mentioned drug microparticles 117g (65%) and self-control suspending agent 59.4g (33%) with taste masking effect mixed, spray into 3.6g flavoring orange essence (2%), make 300 bags of dry suspension, every bag of 600mg.
Wherein the self-control suspending agent in the dry suspension is made by direct powder coating method: microcrystalline Cellulose is placed tangent line spray fluid bed, adopt blower fan frequency 30Hz, 60 ℃ of inlet temperature, atomizing pressure 0.05MPa, rotary speed 500rpm, hydrojet speed 6g/min, microgranule is heated to 55 ℃, the aqueous solution (1g/100ml) of sodium carboxymethyl cellulose is sprayed onto on the microcrystalline Cellulose with atomizing lance, gets final product.
Embodiment 10
Ranitidine 380g (95%), starch 8g (2%) and Pulvis Talci 0.24g (0.06%) are mixed with high shear process by doubly mensuration, place tangent line spray fluid bed, adopt blower fan frequency 20Hz, 36 ℃ of inlet temperature, atomizing pressure 0.15MPa, rotary speed 300rpm, hydrojet speed 6g/min, material is heated to 32 ℃, 3g/100ml hydroxypropyl methylcellulose (viscosity is 50cPs) aqueous solution (containing hydroxypropyl methylcellulose 11.76g (2.94%)) is sprayed onto on the dry blend thing of heating, make the formation drug microparticles, it is dry to heat up, and promptly gets the ranitidine drug microparticles.The ranitidine medicament contg is 95%, and particle diameter is 60～240 μ m, 38 ° of angle of reposes, and the degree of compression 12%, the tablet that friability 10%, microgranule are made is than the tablet tensile strength height made from crude drug under the condition.
Connect aforementioned preparation process, in tangent line spray fluid bed, adopt blower fan frequency 15Hz, 60 ℃ of inlet temperature, atomizing pressure 0.05MPa, rotary speed 200rpm, feed liquor speed 3g/min, drug microparticles are heated to 55 ℃, will
L30D 150g (contained solid masses accounts for coating 60%), triethyl citrate 37.5g (accounting for coating 15%) and Pulvis Talci 62.5g (accounting for coating 25%) are dispersed in the coating solution (mass fraction of solids is 20%) that forms in the water and are sprayed onto on the drug microparticles, 20% stop to increasing weight, dry aging, the ranitidine drug microparticles that promptly obtains having the taste masking effect.Coating accounts for microgranule total amount 16.7%, and particle diameter is 100～250 μ m; 35 ° of angle of reposes, the degree of compression 10%, friability 2% has tablet that this microgranule of taste masking effect makes than with crude drug under the condition and the tablet tensile strength height made of the drug microparticles of coating not.
Above-mentioned drug microparticles 175g (70%), microcrystalline Cellulose 37.5g (15%), mannitol 15g (6%), polyvinylpolypyrrolidone 20g (8%) and magnesium stearate 2.5g (1%) with taste masking effect mixed, make 1000, every 0.25g.The oral cavity disintegration tablet that makes is the 40s disintegrate in mouth, no grittiness, no bitterness.To the external stripping of ranitidine (oar method) 40min stripping 95%.
Above-mentioned drug microparticles 117g (65%) and self-control suspending agent 59.4g (33%) with taste masking effect mixed, spray into 3.6g flavoring orange essence (2%), make 300 bags of dry suspension, every bag of 600mg.
Above-mentioned self-control suspending agent can be made by the granule coating method: microcrystalline Cellulose is placed tangent line spray fluid bed, adopt blower fan frequency 15Hz, 35 ℃ of inlet temperature, atomizing pressure 0.25MPa, rotary speed 250rpm, hydrojet speed 5g/min, material is heated to 32 ℃, and 3g/100ml hydroxypropyl methylcellulose (50cPs) aqueous solution is sprayed onto on the microcrystalline Cellulose, makes the formation microgranule, grow to 80～120 μ m, drying; Then adopt blower fan frequency 25Hz, 45 ℃ of inlet temperature, atomizing pressure 0.05MPa, rotary speed 100rpm, hydrojet speed 6g/min, microgranule is heated to 40 ℃, with aqueous solution (5g/100ml) spraying of sodium carboxymethyl cellulose, grow to 80～180 μ m, drying gets final product.
Claims (18)
1. drug microparticles is characterized in that: it contains 75～95% medicine, 2～22% diluent, 0.06～0.5% fluidizer and 1.5～3.5% binding agent; Percentage ratio is mass percent.
2. drug microparticles as claimed in claim 1 is characterized in that: the surface of described drug microparticles coats one deck coating again; The content of described coating accounts for 5～20% of whole drug microparticles quality; Described coating contains 54～85% coating material, 5～35% antiplastering aid and 10～21% plasticizer; Percentage ratio is mass percent.
3. drug microparticles as claimed in claim 1 is characterized in that:
Described medicine is acetaminophen, aspirin, ibuprofen, cimetidine, diclofenac sodium or ranitidine;
Described diluent is one or more in lactose, starch and the microcrystalline Cellulose;
Described fluidizer is one or more in micropowder silica gel, Pulvis Talci and the magnesium stearate;
Described binding agent is hydroxypropyl methylcellulose and/or polyvinylpyrrolidone.
4. drug microparticles as claimed in claim 2 is characterized in that:
Described coating material be selected from ethyl cellulose, full water ethylcellulose dispersion, homemade IV acrylic resin,
With
In one or more;
Described antiplastering aid is Pulvis Talci and/or glyceryl monostearate;
Described plasticizer is one or more in glycerol, dibutyl phthalate, diethyl phthalate, stearic acid, Polyethylene Glycol, triethyl citrate and the triacetyl glycerine.
5. drug microparticles as claimed in claim 4 is characterized in that: described coating material is the blend of ethyl cellulose and homemade IV acrylic resin, and wherein, the mass ratio of ethyl cellulose and homemade IV acrylic resin is 1: 1～1: 8; Perhaps full water ethylcellulose dispersion and acrylic resin
Blend, wherein, complete contained solid masses and the acrylic resin of water ethylcellulose dispersion
Mass ratio be 1: 1～1: 8.
6. drug microparticles as claimed in claim 1 or 2 is characterized in that: the particle diameter of described drug microparticles is 60～250 μ m.
7. drug microparticles as claimed in claim 6 is characterized in that: the particle diameter of described drug microparticles is 90～180 μ m.
8. drug microparticles as claimed in claim 1 or 2 is characterized in that: be 28～38 ° the angle of repose of described drug microparticles; Described drug microparticles is measured through bulk density and tap density, and the degree of compression of calculating gained is 5～15%; Described drug microparticles is measured by the air-flow method of blowing, and the friability of gained is 1～10%; Under the same conditions, the tensile strength of the tablet of being made by described drug microparticles is higher than the tensile strength of the tablet of being made by medicine material medicine of the same race.
9. the preparation method of drug microparticles as claimed in claim 1, it is characterized in that it comprises the steps: medicine material powder, diluent, fluidizer are mixed with high shear process by doubly mensuration, place tangent line spray fluid bed, make its fluidisation and be heated to 24～35 ℃; The aqueous solution of binding agent is sprayed onto on the dry blend thing of medicine material powder, diluent and fluidizer by atomizing lance, makes it form drug microparticles, drying gets final product.
10. the preparation method of drug microparticles as claimed in claim 2 is characterized in that it comprises the steps:
(1) medicine material powder, diluent, fluidizer are mixed with high shear process by doubly mensuration, place tangent line spray fluid bed, make its fluidisation and be heated to 24～35 ℃; The aqueous solution of binding agent is sprayed onto on the dry blend thing of medicine material powder, diluent and fluidizer by atomizing lance, makes it form drug microparticles, drying;
(2) in tangent line spray fluid bed, make the drug microparticles fluidisation and be heated to 35～55 ℃, coating material, antiplastering aid and plasticizer are dispersed in the coating solution that forms in water or the ethanol water and are sprayed onto on the microgranule, to increasing weight 5～25% by atomizing lance, dry aging, get final product.
11. as claim 9 or 10 described methods, it is characterized in that: in the claim 9 or in the step of claim 10 (1), the operating condition of described tangent line spray fluid bed is: the blower fan frequency is 15～30Hz; Inlet temperature is 30～40 ℃; Temperature of charge is 24～35 ℃; The rotational frequency of rotating disk is 120～500rpm; The atomizing pressure of atomizing lance is 0.05～0.25MPa; Hydrojet speed is 3～6g/min.
12. method as claimed in claim 10 is characterized in that: in the step (2), the operating condition of described tangent line spray fluid bed is: the blower fan frequency is 15～30Hz; Inlet temperature is 40～60 ℃; Temperature of charge is 35～55 ℃; The rotational frequency of rotating disk is 100～200rpm; The atomizing pressure of atomizing lance is 0.05～0.25MPa; The hydrojet speed of coating solution is 2～6g/min.
13. contain the preparation of drug microparticles as claimed in claim 1 or 2.
14. preparation as claimed in claim 13 is characterized in that: described preparation is oral cavity disintegration tablet, dry suspension or granule.
15. preparation as claimed in claim 14 is characterized in that: described oral cavity disintegration tablet contains 31～70% drug microparticles as claimed in claim 1 or 2,21～60% tablet diluent, 2～8% disintegrating agent and 0.5～1% lubricant.
16. oral disintegrating tablet formulation as claimed in claim 15 is characterized in that:
Described tablet diluent is one or more in microcrystalline Cellulose, lactose, sorbitol and the mannitol, perhaps self-control tablet diluent: lactose and the microcrystalline Cellulose mass ratio with 2: 1～5: 1 is mixed for making by following method, place tangent line spray fluid bed, make its fluidisation and be heated to 24～35 ℃; The aqueous solution of binding agent is sprayed onto on the dry blend thing of lactose and microcrystalline Cellulose by atomizing lance, makes it form granule, when granule grows to 60～250 μ m, dry getting final product; The operating parameter of wherein concrete fluid bed is described with claim 11;
Described disintegrating agent is one or more in polyvinylpolypyrrolidone, sodium carboxymethyl cellulose and the crosslinked carboxymethyl fecula sodium;
Described lubricant is a magnesium stearate.
17. preparation as claimed in claim 14 is characterized in that: described dry suspension contains 50～65% drug microparticles as claimed in claim 1 or 2,33～48% suspending agents and 1～2% essence.
18. dried mixed suspension preparation as claimed in claim 17, it is characterized in that: described suspending agent is one or more in microcrystalline Cellulose, sodium carboxymethyl cellulose and the hydroxypropyl methylcellulose, perhaps is according to any the self-control suspending agent that makes in following two kinds of methods:
(1) direct powder coating method: microcrystalline Cellulose is placed tangent line spray fluid bed, make its fluidisation and be heated to 35～55 ℃, the aqueous solution of sodium carboxymethyl cellulose is sprayed onto on the microcrystalline Cellulose with atomizing lance, and the operating parameter of wherein concrete fluid bed is described with claim 12;
(2) granule coating method: microcrystalline Cellulose is placed tangent line spray fluid bed, and fluidisation also is heated to 24～35 ℃, and the aqueous solution of binding agent is sprayed onto on the microcrystalline Cellulose, make the formation granule, grow to 60～150 μ m, drying, concrete fluidized bed process parameter is described with claim 11; With grain fluidized and be heated to 35～55 ℃, the spraying of the aqueous solution of reuse sodium carboxymethyl cellulose makes granule grow to 80～250 μ m, drying, and concrete fluidized bed process step is described with claim 12.
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