CN1245956C - Method for producing oral administration delay-control release medicine micro balls - Google Patents
Method for producing oral administration delay-control release medicine micro balls Download PDFInfo
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- CN1245956C CN1245956C CN 200410068840 CN200410068840A CN1245956C CN 1245956 C CN1245956 C CN 1245956C CN 200410068840 CN200410068840 CN 200410068840 CN 200410068840 A CN200410068840 A CN 200410068840A CN 1245956 C CN1245956 C CN 1245956C
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- verapamil hydrochloride
- delay
- controlled release
- spray drying
- microgranule
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- 239000003814 drug Substances 0.000 title claims abstract description 30
- 239000011806 microball Substances 0.000 title abstract description 6
- 238000004519 manufacturing process Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 32
- 239000000463 material Substances 0.000 claims abstract description 22
- 238000001694 spray drying Methods 0.000 claims abstract description 22
- 238000002360 preparation method Methods 0.000 claims abstract description 18
- DOQPXTMNIUCOSY-UHFFFAOYSA-N [4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl]-[2-(3,4-dimethoxyphenyl)ethyl]-methylazanium;chloride Chemical compound [H+].[Cl-].C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 DOQPXTMNIUCOSY-UHFFFAOYSA-N 0.000 claims description 54
- 229960000881 verapamil hydrochloride Drugs 0.000 claims description 54
- 238000013270 controlled release Methods 0.000 claims description 33
- 239000004005 microsphere Substances 0.000 claims description 23
- 239000007788 liquid Substances 0.000 claims description 22
- 239000004531 microgranule Substances 0.000 claims description 22
- 239000011248 coating agent Substances 0.000 claims description 20
- 238000000576 coating method Methods 0.000 claims description 20
- 239000007787 solid Substances 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 239000006199 nebulizer Substances 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 4
- 230000001934 delay Effects 0.000 claims description 4
- 239000012530 fluid Substances 0.000 claims description 4
- 238000005243 fluidization Methods 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 238000005469 granulation Methods 0.000 claims description 4
- 230000003179 granulation Effects 0.000 claims description 4
- 239000002245 particle Substances 0.000 claims description 4
- 239000004014 plasticizer Substances 0.000 claims description 4
- 239000003361 porogen Substances 0.000 claims description 4
- 239000007921 spray Substances 0.000 claims description 4
- 239000000080 wetting agent Substances 0.000 claims description 4
- 238000009477 fluid bed granulation Methods 0.000 claims description 2
- 238000005516 engineering process Methods 0.000 abstract description 12
- 239000011859 microparticle Substances 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 206010067484 Adverse reaction Diseases 0.000 abstract 1
- 230000006838 adverse reaction Effects 0.000 abstract 1
- 230000033764 rhythmic process Effects 0.000 abstract 1
- 230000001360 synchronised effect Effects 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 229940079593 drug Drugs 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 8
- 229920001661 Chitosan Polymers 0.000 description 7
- 229920003159 Eudragit® RS 100 Polymers 0.000 description 7
- 229920002301 cellulose acetate Polymers 0.000 description 7
- 238000000889 atomisation Methods 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229920003134 Eudragit® polymer Polymers 0.000 description 4
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 4
- 229920002535 Polyethylene Glycol 1500 Polymers 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000003094 microcapsule Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 2
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 239000001069 triethyl citrate Substances 0.000 description 2
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 2
- 235000013769 triethyl citrate Nutrition 0.000 description 2
- 229960001722 verapamil Drugs 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000013563 matrix tablet Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides a preparation method of an oral administration delay-control release medicine micro ball, which belongs to the field of medical preparation. The method is characterized in that medicine and suitable auxiliary materials are dissolved or suspended and mixed in a microencapsulated material solution with the functions of slow release and control release, medicine micro particles are prepared by a spray drying method, and the medicine micro particles are coated to prepare the delay-control release medicine micro ball. The present invention can be prepared into various oral administration preparations by suitable preparation methods. The oral administration delay-control release medicine micro ball has the characteristic that the medicine is not immediately released after entering a human body but is stably and continuously released at a prearranged speed rate after a period of preset delay time, and the purpose of control release administration by selecting time can be obtained. A medicine releasing technology which is synchronous with physiological rhythm is used by aiming at some diseases with diurnal rhythmicity, a speed control release system is combined with a medicine releasing system by time selecting control, and an optimal therapeutic effect and minimal adverse reaction are achieved.
Description
Technical field
The present invention relates to medical technical field, it is to utilize spray drying to prepare oral time-delay in conjunction with art for coating in definite saying---a kind of method of controlled release verapamil hydrochloride microgranule (microcapsule or microsphere).
Background technology
Some disease of discovered in recent years demonstrates the rhythmicity characteristics, as the dyspnea of asthmatic patient outbreak be the daytime-change night, a large amount of clinical observations find that be the high-incidence season of asthma morning; The situation of hypertension and myocardial infarction morbidity is also similar.Drug-supplying system discharges and onset between in due course by the control medicine when selecting, and can prevent and treat the outbreak of diseases such as asthma and myocardial infarction.Drug-delivery preparation does not generally discharge medicine immediately when selecting after entering human body, but through the one predefined period (time lag).Time lag is the key of this technology, and the most frequently used method is the purpose that reaches time lag by substrate or outer release-controlled film in the prescription design.The release technology has obtained very big development when selecting over past ten years, from film controlled release preparation the earliest, comprise: coating capsule, coated tablet, double-deck matrix tablet, osmotic pumps, and afterwards timing plug pulse capsule, pulse patch and subcutaneous implanted pulse agent, the mode of control time lag is more and more diversified.But except the peplos osmotic pumps, drug-supplying system adopted the pulsed administration when majority was selected, promptly after delay after a while, medicine discharges suddenly with the form of pulse, can't reach the purpose of controlling administration at the time lag after date, blood drug level rises and falls very big, and " peak valley " phenomenon is arranged.When blood drug level is high (peak), may exceeds the Cmax of treatment window (the blood drug level interval that refers to medicine performance curative effect) and have side effects, even cause poisoning; When blood drug level hangs down (paddy), may be lower than effective minimum treatment concentration, so that can not manifest curative effect, limit broad research and the application in this respect of this technology.Using the preparation of microencapsulation technology delays time---and controlled-release pharmaceutical formulation has broad application prospects, the research of drug microparticles preparation method is a lot of at present, the research of relevant drug microparticles coating also has report, but does not still have the report of oral administration delay-control release medicine micro balls preparation method.
Summary of the invention
The objective of the invention is: will control administration the time and the speed controlling administration combines, adopt a kind of technology new method simple, easy and control to prepare oral time-delay---the microgranule (microcapsule or microsphere) of controlled release verapamil hydrochloride, the treatment that this will help having the cardiovascular disease of daily rhythmicity reaches optimum curative effect and minimum untoward reaction.Add excipient substance, the formulation method by suitable also can be made into various oral controlled slow-release preparations.
The invention is characterized in that it contains following steps successively:
(1) forming described mouthful by following weight percent comparison delays time---and each component of controlled release verapamil hydrochloride microsphere is prepared burden:
Verapamil hydrochloride: 2.5～7.0%
Microencapsulation material: 15～32%
Coating material: 65～80%; Adjuvant, porogen or plasticizer or wetting agent or antiplastering aid: surplus;
(2) reach process conditions according to the following steps, with spray drying method for preparation verapamil hydrochloride microgranule; Be particle diameter the verapamil hydrochloride granule of 1～90 μ m and proper auxiliary materials by the total solids content dissolving of said ratio and following feed liquid or be suspended in the microencapsulation material solution of slow/controlled release effect, be made into homogeneous or homodisperse spray drying feed liquid; Then at 75kPa～250kPa nebulizer pressure, 55 ℃～140 ℃ inlet temperatures, 45 ℃～95 ℃ outlet temperatures, the charging rate of 4～12ml/min, 2.2 spray drying granulation under the condition of the total solids content of the feed liquid of～6.0% (weight/volume) is made the verapamil hydrochloride microgranule;
(3) reach process conditions according to the following steps, the verapamil hydrochloride microgranule is carried out coating, make oral with spray drying method
Time-delay---controlled release verapamil hydrochloride microsphere:
Under the condition of high-speed stirred, the verapamil hydrochloride microgranule that step (2) is made adds in the coating material solution and is uniformly dispersed, and obtains the spray drying feed liquid; Then at 20kPa～50kPa nebulizer pressure, 55 ℃～140 ℃ inlet temperatures, 45 ℃～95 ℃ outlet temperatures, the charging rate of 4～8ml/min, 3.0 under the condition of the total solids content of the feed liquid of～12% (weight/volume), make oral time-delay with spray drying method---controlled release verapamil hydrochloride microsphere.
Feature of the present invention is that also it contains following steps successively:
(1) forming described mouthful by following weight percent comparison delays time---and each component of controlled release verapamil hydrochloride microsphere is prepared burden:
Verapamil hydrochloride: 2.5～7.0%
Microencapsulation material: 15～32%
Coating material: 65～80%;
Adjuvant, porogen or plasticizer or wetting agent or antiplastering aid: surplus;
(2) reach process conditions according to the following steps, with spray drying method for preparation verapamil hydrochloride microgranule;
Be particle diameter the verapamil hydrochloride granule of 1～90 μ m and proper auxiliary materials by the total solids content dissolving of said ratio and following feed liquid or be suspended in the microencapsulation material solution of slow/controlled release effect, be made into homogeneous or homodisperse spray drying feed liquid; Then at 20kPa～75kPa nebulizer pressure, 55 ℃～140 ℃ inlet temperatures, 45 ℃～95 ℃ outlet temperatures, the charging rate of 4～12ml/min, 5.0 spray drying granulation under the condition of the total solids content of the feed liquid of～12% (weight/volume) is made the verapamil hydrochloride microgranule;
(3) reach process conditions according to the following steps with fluid bed granulation process, the verapamil hydrochloride microgranule that step (2) is made carries out coating, makes oral time-delay---controlled release verapamil hydrochloride microsphere:
By said ratio configuration coating material solution; Again medicine carrying microgranule being placed miniature fluid bed, is 0.5mm～1mm with end spray method at nozzle diameter, and the fluidisation air quantity is 100～150m
3/ h, inlet temperature is 35～55 ℃, and temperature is 30 ℃～40 ℃ in the bed, and atomizing pressure is 150kPa～200kPa, under hydrojet speed 1.2～2.4g/min process conditions, medicine carrying microgranule is carried out coating, makes oral time-delay---controlled release verapamil hydrochloride microsphere.
The present invention can delay time in external gastrointestinal tract model---and controlled release drug, the formulation method by suitable can be made into various oral formulations.
Advantage of the present invention is: will control administration the time and the speed controlling administration combines, use time-delay---the controlled release verapamil hydrochloride microgranule (microcapsule or microsphere) of this method preparation, it is controlled to have delay time, the characteristics that the verapamil hydrochloride rate of release is controlled, and technology is simple, easy and control, can produce by batch in a large number.
Description of drawings:
Fig. 1 a is the stereoscan photograph of embodiment 1.
The stereoscan photograph of Fig. 1 b embodiment 2
The cumulative in vitro release profiles of Fig. 2 embodiment 1,2
The specific embodiment:
Below in conjunction with embodiment the present invention is further illustrated, embodiment illustrates time-delay provided by the invention by adopting different microencapsulation prescription and technology---the preparation method of controlled release verapamil hydrochloride microgranule, but not only be confined to listed
Embodiment.
Embodiment 1:
The chitosan of verapamil hydrochloride-Eudragit RS100 microsphere (VPH/CS/RS100) composition
Verapamil hydrochloride 0.2g
Chitosan 2.0g
Eudragit?RS100 4.4g
0.1mol/L acetum 100ml
Ethyl acetate 220ml
Technology
1. verapamil hydrochloride and chitosan are dissolved in the acetum of 0.1mol/L, are made into uniform solution as spray-dired feed liquid.Spray-dired operating parameter is: 140 ℃ of hot-air inlets temperature, hot blast rate 0.7m
3/ min, 95 ℃ of outlet temperatures, feed rate 12mL/min, atomisation pressure 250kPa.
2. Eudragit RS100 is dissolved in and is made into 2% solution in the ethyl acetate.Under the condition of high-speed stirred, in the chitosan microball adding solution with verapamil hydrochloride, be uniformly dispersed.With the feed liquid spray drying that obtains, operating parameter is: 80 ℃ of hot-air inlets temperature, hot blast rate 0.5m
3/ min, 65 ℃ of outlet temperatures, feed rate 8mL/min, atomisation pressure 50kPa.
The release in vitro degree is measured
Adopt the device of dissolution method (2000 editions two appendix XC second methods of Chinese Pharmacopoeia), according to drug release determination method (2000 editions two appendix XD first methods of Chinese Pharmacopoeia), with water 900ml is solvent, and rotating speed is 100r/min, and the microsphere that makes is carried out drug release determination.In each time point sampling, adopt ultraviolet spectrometry light photometry to measure trap respectively, and calculate burst size at the wavelength of 268nm.
Release in vitro result
Delay time 4h
Controlled release time 20h
Linear coefficient R of controlled release stage
2=0.9973
Embodiment 2:
Verapamil hydrochloride cellulose acetate-Eudragit RS100 microsphere (VPH/CA/RS100)
Composition
Verapamil hydrochloride 0.6g
Cellulose acetate 2.4g
PEG1500 0.06g
Eudragit?RS100 6.0g
Ethyl acetate 50ml
Ethanol 75ml
Technology
1. cellulose acetate and PEG1500 are dissolved in the ethyl acetate, are made into homogeneous solution.Under the condition of high-speed stirred, verapamil hydrochloride is joined in the ethyl acetate solution of cellulose acetate, make spray-dired feed liquid.Spray-dired operating parameter is: 55 ℃ of hot-air inlets temperature, hot blast rate 0.7m
3/ min, 45 ℃ of outlet temperatures, feed rate 4mL/min, atomisation pressure 75kPa.
2. Eudragit RS100 is dissolved in and is made into 8% solution in the ethanol.Under the condition of high-speed stirred, in the cellulose acetate microcapsule adding solution with verapamil hydrochloride, be uniformly dispersed.With the feed liquid spray drying that obtains, operating parameter is: 70 ℃ of hot-air inlets temperature, hot blast rate 0.5m
3/ min, 55 ℃ of outlet temperatures, feed rate 4mL/min, atomisation pressure 20kPa.
The release in vitro degree is measured
With embodiment 1
Release in vitro result
Delay time 4h
Controlled release time 20h
Linear coefficient R of controlled release stage
2=0.9985
Embodiment 3:
The chitosan of verapamil hydrochloride-Eudragit RS100 microsphere (VPH/CS/RS100)
Composition
Verapamil hydrochloride 0.5g
Chitosan 2.0g
Eudragit?RS100 10.0g
Triethyl citrate 0.5g
0.1mol/L acetum 50ml
Acetone 200ml
Technology
1. verapamil hydrochloride and chitosan are dissolved in the acetum of 0.1mol/L, are made into uniform solution as spray-dired feed liquid.Spray-dired operating parameter is: 140 ℃ of hot-air inlets temperature, hot blast rate 0.7m
3/ min, 95 ℃ of outlet temperatures, feed rate 12mL/min, atomisation pressure 75kPa.
2. Eudragit RS100 and triethyl citrate are dissolved in and are made into the solution that contains polymer 5% in the acetone.Medicine carrying microballoons is placed miniature fluid bed, and coating adopts end spray method, nozzle diameter 0.5mm, fluidisation air quantity 150m
3H
-1, 35 ℃ of inlet temperature, temperature 30 in the bed, atomizing pressure 150kPa, hydrojet speed 2.4gmin
-1
Release in vitro result
Delay time 6h
Controlled release time 8h
Linear coefficient R of controlled release stage
2=0.9987
Embodiment 4:
Verapamil hydrochloride cellulose acetate-EudragiIt RSl00 microsphere (VPH/CA/RSl00)
Composition
Verapamil hydrochloride 1.2g
Cellulose acetate 4.8g
PEG1500 0.12g
Eudragit RSl00 aqueous dispersion (polymer content 30%) 40ml
Ethyl acetate 50ml
Distilled water 80ml
Technology
L. cellulose acetate and PEG1500 are dissolved in the ethyl acetate, are made into homogeneous solution.Under the condition of high-speed stirred, verapamil hydrochloride is joined in the ethyl acetate solution of cellulose acetate, make spray-dired feed liquid.Spray-dired operating parameter is: 55 ℃ of hot-air inlets temperature, hot blast rate 0.7m
3/ min, 45 ℃ of outlet temperatures, feed rate 4mL/min, atomisation pressure 20kPa.
2. medicine carrying microballoons is placed miniature fluid bed, it is 10% coating solution that Eudragit RS100 aqueous dispersion (polymer content 30%) is diluted with water to polymer content, and coating adopts end spray method, nozzle diameter 0.5mm, fluidisation air quantity 100m
3H
-1, 55 ℃ of inlet temperature, temperature is 40 ℃ in the bed, atomizing pressure 200kPa, hydrojet speed 1.2gmin
-1
The release in vitro degree is measured
With embodiment 1
Release in vitro result
Delay time 6h
Controlled release time 18h
Linear coefficient R of controlled release stage
2=0.9998
Claims (2)
1. oral time-delay---the preparation method of controlled release verapamil hydrochloride microsphere is characterized in that it contains following steps successively:
(1) described oral time-delay---each component of controlled release verapamil hydrochloride microsphere is prepared burden by following weight percent comparison composition:
Verapamil hydrochloride: 2.5～7.0%
Microencapsulation material: 15～32%
Coating material: 65～80%;
Adjuvant, porogen or plasticizer or wetting agent or antiplastering aid: surplus;
(2) reach process conditions according to the following steps, use spray drying method for preparation verapamil hydrochloride microgranule:
Be particle diameter the verapamil hydrochloride granule of 1～90 μ m and proper auxiliary materials by the total solids content dissolving of said ratio and following feed liquid or be suspended in the microencapsulation material solution of slow/controlled release effect, be made into homogeneous or homodisperse spray drying feed liquid; Then at 75kPa～250kPa nebulizer pressure, 55 ℃～140 ℃ inlet temperatures, 45 ℃～95 ℃ outlet temperatures, the charging rate of 4～12ml/min, 2.2 spray drying granulation under the condition of the total solids content of the feed liquid of～6.0% weight/volume is made the verapamil hydrochloride microgranule;
(3) reach process conditions according to the following steps, the verapamil hydrochloride microgranule carried out coating, make oral time-delay with spray drying method---controlled release verapamil hydrochloride microsphere:
Under the condition of high-speed stirred, the verapamil hydrochloride microgranule that step (2) is made adds in the coating material solution and is uniformly dispersed, and obtains the spray drying feed liquid; Then at 20kPa～50kPa nebulizer pressure, 55 ℃～140 ℃ inlet temperatures, 45 ℃～95 ℃ outlet temperatures, the charging rate of 4～8ml/min, 3.0 under the condition of the total solids content of the feed liquid of～12% weight/volume, make oral time-delay with spray drying method---controlled release verapamil hydrochloride microsphere.
2. oral time-delay---the preparation method of controlled release verapamil hydrochloride microsphere is characterized in that it contains following steps successively:
(1) forming described mouthful by following weight percent comparison delays time---and each component of controlled release verapamil hydrochloride microsphere is prepared burden:
Verapamil hydrochloride: 2.5～7.0%
Microencapsulation material: 15～32%
Coating material: 65～80%;
Adjuvant, porogen or plasticizer or wetting agent or antiplastering aid: surplus;
(2) reach process conditions according to the following steps, use spray drying method for preparation verapamil hydrochloride microgranule:
Be particle diameter the verapamil hydrochloride granule of 1～90 μ m and proper auxiliary materials by the total solids content dissolving of said ratio and following feed liquid or be suspended in the microencapsulation material solution of slow/controlled release effect, be made into homogeneous or homodisperse spray drying feed liquid; Then at 20kPa～75kPa nebulizer pressure, 55 ℃～140 ℃ inlet temperatures, 45 ℃～95 ℃ outlet temperatures, the charging rate of 4～12ml/min, 5.0 spray drying granulation under the condition of the total solids content of the feed liquid of～12% weight/volume is made the verapamil hydrochloride microgranule;
(3) reach process conditions according to the following steps with fluid bed granulation process, the verapamil hydrochloride microgranule that step (2) is made carries out coating, makes oral time-delay---controlled release verapamil hydrochloride microsphere:
By said ratio configuration coating material solution; Again medicine carrying microgranule being placed miniature fluid bed, is 0.5mm～1mm with end spray method at nozzle diameter, and the fluidisation air quantity is 100～150m
3/ h, inlet temperature is 35～55 ℃, and temperature is 30 ℃～40 ℃ in the bed, and atomizing pressure is 150kPa～200kPa, under hydrojet speed 1.2～2.4g/min process conditions, medicine carrying microgranule is carried out coating, makes oral time-delay---controlled release verapamil hydrochloride microsphere.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410068840 CN1245956C (en) | 2004-07-09 | 2004-07-09 | Method for producing oral administration delay-control release medicine micro balls |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410068840 CN1245956C (en) | 2004-07-09 | 2004-07-09 | Method for producing oral administration delay-control release medicine micro balls |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1586460A CN1586460A (en) | 2005-03-02 |
| CN1245956C true CN1245956C (en) | 2006-03-22 |
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|---|---|---|---|
| CN 200410068840 Expired - Fee Related CN1245956C (en) | 2004-07-09 | 2004-07-09 | Method for producing oral administration delay-control release medicine micro balls |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1879606B (en) * | 2006-05-02 | 2011-12-14 | 沈阳药科大学 | Preparation of novel drug delivery system based on liquid spray method |
| CN103520115B (en) * | 2013-09-27 | 2015-04-22 | 内蒙古医科大学 | Verapamil hydrochloride sustained release microsphere and preparation method thereof |
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