CN101491508B - Preparation method of aspirin Intestine-soluble micro-pill capsules - Google Patents
Preparation method of aspirin Intestine-soluble micro-pill capsules Download PDFInfo
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- CN101491508B CN101491508B CN2009100458023A CN200910045802A CN101491508B CN 101491508 B CN101491508 B CN 101491508B CN 2009100458023 A CN2009100458023 A CN 2009100458023A CN 200910045802 A CN200910045802 A CN 200910045802A CN 101491508 B CN101491508 B CN 101491508B
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- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 title claims abstract description 65
- 229960001138 acetylsalicylic acid Drugs 0.000 title claims abstract description 64
- 239000002775 capsule Substances 0.000 title claims abstract description 29
- 239000006187 pill Substances 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 239000011248 coating agent Substances 0.000 claims abstract description 26
- 238000000576 coating method Methods 0.000 claims abstract description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 6
- 239000000080 wetting agent Substances 0.000 claims abstract description 6
- 239000004014 plasticizer Substances 0.000 claims abstract description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 3
- 238000005507 spraying Methods 0.000 claims description 10
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 8
- 239000008187 granular material Substances 0.000 claims description 8
- 239000004925 Acrylic resin Substances 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 229920000178 Acrylic resin Polymers 0.000 claims description 5
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 230000001476 alcoholic effect Effects 0.000 claims description 5
- 229960003943 hypromellose Drugs 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 239000007921 spray Substances 0.000 claims description 5
- 239000001069 triethyl citrate Substances 0.000 claims description 5
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 5
- 235000013769 triethyl citrate Nutrition 0.000 claims description 5
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 claims description 4
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 4
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 4
- 150000005690 diesters Chemical class 0.000 claims description 3
- 239000002702 enteric coating Substances 0.000 claims description 3
- 238000009505 enteric coating Methods 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 229960003511 macrogol Drugs 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- 238000000034 method Methods 0.000 abstract 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 abstract 1
- 230000002349 favourable effect Effects 0.000 abstract 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 abstract 1
- 229940069328 povidone Drugs 0.000 abstract 1
- 239000008213 purified water Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 206010008190 Cerebrovascular accident Diseases 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- 208000025865 Ulcer Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 231100000397 ulcer Toxicity 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010061297 Mucosal erosion Diseases 0.000 description 3
- 206010061298 Mucosal haemorrhage Diseases 0.000 description 3
- 229920003081 Povidone K 30 Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 206010061623 Adverse drug reaction Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 208000007814 Unstable Angina Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 210000001156 gastric mucosa Anatomy 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 206010002388 Angina unstable Diseases 0.000 description 1
- 206010003226 Arteriovenous fistula Diseases 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 206010050902 Postoperative thrombosis Diseases 0.000 description 1
- 208000007718 Stable Angina Diseases 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000003907 antipyretic analgesic agent Substances 0.000 description 1
- 229940067132 aspirin 25 mg Drugs 0.000 description 1
- 229940085350 aspirin 75 mg Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- -1 benzoic acid (2-ethanoylhydroxybenzoic acid) Chemical compound 0.000 description 1
- 229960003328 benzoyl peroxide Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 108010017796 epoxidase Proteins 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
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- 230000009965 odorless effect Effects 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000009861 stroke prevention Effects 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a method for preparing an aspirin enteric-coated micro-pill capsule. The method comprises that: the method selects 50 to 80g of aspirin with 0 to 300 microns, uses 1 to 5g of povidone and 0.1 to 0.8g of hydroxypropyl methylcellulose and uses 5 percent ethanol solution in percentage by mass as a wetting agent to prepare an active pill core; the method selects 3 to 60g of a coating auxiliary material with enteric-coated function, 0.3 to 6g of a plasticizer, 0.01 to 0.06g of a releasing agent, 0.1 to 0.5g of talcum powder and 5 to 30g of purified water to prepare a solution for coating; and a micro-pill is directly filled to prepare the aspirin enteric-coated micro-pill capsule. The preparation method is simple, low in cost, beneficial for environment and favorable for industrialized production; and the prepared aspirin capsule has good stability and obviously reduces generation of side effect.
Description
Technical field
The invention belongs to the preparation field of aspirin capsule, particularly relate to a kind of preparation method of aspirin Intestine-soluble micro-pill capsules.
Background technology
Aspirin (Aspirin) has another name called aspirin (Acetylsalicylic Acid), and chemistry is by name: 2-(acetoxyl group) benzoic acid (2-ethanoylhydroxybenzoic acid), molecular formula: C
9H
8O
4, molecular weight: 180.16.Structural formula is:
Aspirin is a kind of white crystals or crystalline powder; Odorless or little band acetic acid stink, little acid of distinguishing the flavor of; Meet the i.e. slowly hydrolysis of dampness.Fusing point is 135 ℃.This product is easily molten in ethanol, dissolves slightly soluble in water or absolute ether in chloroform or ether; In sodium hydroxide solution or sodium carbonate liquor, dissolve, but decompose simultaneously.
Aspirin is time-honored antipyretic analgesic, and it is born on March 6th, 1899.The luxuriant and rich with fragrance Huffman of Germanization scholar in 1898 synthesizes, and is made referrals to clinically in 1899 by Dierser, and is named as aspirin (Aspirin).Up to the present, aspirin has been used a century, becomes one of three big classical medicines on the medical history, and it is still most widely used in the world analgesic, analgesia and anti-inflammatory agent so far, also be as a comparison with the standard preparation of estimating other drug.The sixties in last century, discover that aspirin has antithrombotic effect in vivo, it can suppress hematoblastic release reaction, suppresses hematoblastic gathering, and this is relevant with the minimizing that TXA2 generates.Be used to prevent the outbreak of cardiovascular and cerebrovascular disease clinically.
This product has inhibitory action to platelet aggregation, stops thrombosis, clinically can be used for preventing temporal cerebral ischemia seizure, myocardial infarction, atrial fibrillation, Cardiac valve prosthesis, arteriovenous fistula or other postoperative thrombosis.Also can be used for treating unstable angina pectoris.
A large amount of clinical trials shows, concerning most patients, comprises chronic stable or unstable angina patient, can effectively reduce aspirin 75mg/ day acute myocardial infarction and dead danger take place.This dosage also can reduce transient cerebral ischemic attack patient apoplexy and dead incidence rate.The stroke prevention in Europe studies show that previously have the patient of transient cerebral ischemic attack and apoplexy medical history to use aspirin 25mg, every day 2 times, promptly can reduce apoplexy or dead danger 50mg/ day.Clinical practice proves that even the patient takes than the higher aspirin of dosage in the table, curative effect can further not increase, but the generation of side effect increases greatly.Therefore in the various thrombotic disease of treatment, the patient should use minimum effective dose, that is prolonged application 50-160mg/ day, and to reach greatest treatment efficacy, it is minimum that toxic and side effects then reduces to, and this is only the optimal dose that the patient takes aspirin.
Aspirin has coronary artery dilator and cerebrovascular effect, and it is synthetic at liver to fail the anticoagulant proenzyme, can suppress the activity of epoxidase and reduce the formation of thromboxane A2, stops platelet aggregation, makes it be difficult for emitting thrombin, has certain blood coagulation resisting function.Now be used for the auxiliary treatment and the prophylactic of cardiovascular disease and apoplexy clinically in a large number, take with the doses over long periods of 100mg/ day.
Aspirin can cause gastric mucosal erosion, hemorrhage and ulcer etc.Most of patients clothes median dose aspirin a couple of days, promptly see the Fecal Occult Blood Testing positive; Long-term patient taking this drug Peptic Ulcers is sent out the rate height.Except that the acidity of medicine directly caused the gastric mucosa damage, injecting drug use also can take place.Aspirin can see through gastric epithelial lipoprotein rete, destroys the protective effect of lipoprotein membrane, so gastric acid just reversibly permeates into damaging cells in the tissue, it is damaged and hemorrhage to cause blood capillary.Recently find prostaglandin for safeguarding that the gastric mucosa tool has certain effect, and aspirin has proved and can stop the synthetic of prostaglandin, gastric epithelial has been come off increase and surpass renewal speed, increased the weight of the degree of ulcer, the stomach mucus is reduced.
Therefore, in order to overcome the side effect of taking aspirin for a long time and being produced, the present invention has carried out further research to the aspirin capsule.
Summary of the invention
Technical problem to be solved by this invention provides a kind of preparation method of aspirin Intestine-soluble micro-pill capsules, and preparation method of the present invention is simple, and cost is low, and is useful to environment, helps suitability for industrialized production; The aspirin capsule of the present invention preparation has good stable, and has reduced significantly and taken aspirin for a long time and cause drug side effectes such as gastric mucosal erosion, hemorrhage and ulcer.
The preparation method of a kind of aspirin Intestine-soluble micro-pill capsules of the present invention comprises:
(1) preparation of active medicine ball core
Get the aspirin 50-80g of 0-300 micron, use polyvidone 1-5g, hypromellose 0.1-0.8g, with mass percent concentration be 5% alcoholic solution as wetting agent, make active ball core;
(2) enteric coating
Get coating adjuvant 3-60g, the plasticizer 0.3-6g, releasing agent 0.01-0.06g, Pulvis Talci 0.1-0.5g and the pure water 5-30g that contain the enteric function and be mixed with solution, carry out coating and drying, the fluidized coating parameter is: the coating jar is preheated to 38 ℃, spraying, 25-55 ℃ of coating temperature, atomizing pressure 0.2-0.45MPa, spray liquid flow 2-80ml/min is after spraying finishes, continue dry 20min, granulate is got the directly micropill of 400-1000 micron of ball, promptly;
(3) micropill is directly filled, be prepared into aspirin Intestine-soluble micro-pill capsules.
The coating adjuvant that contains the enteric function in the described step (2) is polyacrylic resin (Youteqi L30D55), II acrylic resin or III acrylic resin etc.;
Plasticizer in the described step (2) is selected from one or both the mixture in glyceryl monostearate, triethyl citrate, Macrogol 200-20000, certain herbaceous plants with big flowers diacid fourth diester, the diethyl phthalate;
Releasing agent in the described step (2) is polysorbas20-100 or the 20-100 of class of department etc.;
The content 75%-85% of aspirin in the described aspirin Intestine-soluble micro-pill.
The enteric-coating material Youteqi L30D55 that the present invention adopts, have good film property, plasticity, made film-coat is colourless, tasteless, flexible good, has good crack resistance, very stable under heat, light, air and certain humiture, provide good guarantee to the quality stability in the product shelf life, according to study on the stability test, in the free salicylic acid of aspirin Intestine-soluble micro-pill capsules 3 years＜3.0%.Simultaneously, because meeting water, easily decomposes aspirin, so spraying-exsiccant balance is extremely important; Tween 80 also is extremely important as releasing agent.
Beneficial effect
(1) preparation method of the present invention is simple, and cost is low, and is useful to environment, helps suitability for industrialized production;
(2) aspirin Intestine-soluble micro-pill capsules of the present invention preparation has good stable, and has reduced significantly and taken aspirin for a long time and cause drug side effectes such as gastric mucosal erosion, hemorrhage and ulcer.
The specific embodiment
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after the content of having read the present invention's instruction, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Embodiment 1
(1) get the aspirin 50g of 0-300 micron, with 30 POVIDONE K 30 BP/USP 30 1-3g, hypromellose 0.1-0.5g makes 5% alcoholic solution as wetting agent, makes active ball core.Dry.Granulate.Get the aspirin micropill;
(2) get Youteqi L30D55 10-50g, triethyl citrate 0.2-1g, glyceryl monostearate 0.1-0.3g, tween 80 0.01-0.03g, Pulvis Talci 0.1-0.4g, pure water 5-30g are mixed with solution, carry out coating,
The fluidized coating parameter is: the coating jar is preheated to 38 ℃, spraying, and 30 ℃ of coating temperature, atomizing pressure 0.2MPa, spray liquid flow 25ml/min, spraying continues dry 20min after finishing, and granulate is got the directly micropill of 400-1000 micron of ball; After testing, aspirin content 82.05%, sundry item meets quality standard.
(3) micropill is directly filled, make aspirin Intestine-soluble micro-pill capsules.
After testing, aspirin content is labelled amount 95-105%, and sundry item meets the capsule quality standard.
Embodiment 2
(1) get the aspirin 80g of 0-300 micron, use 30 POVIDONE K 30 BP/USP 302-5g, hypromellose 0.2-0.8g makes 5% alcoholic solution as wetting agent, makes active ball core.Dry.Granulate.Get the aspirin micropill;
(2) get Youteqi L30D55 20-60g, triethyl citrate 0.5-1.5g, glyceryl monostearate 0.2-0.5g, tween 80 0.02-0.04g, Pulvis Talci 0.2-0.5g, pure water 5-30g are mixed with solution, carry out coating, the fluidized coating parameter is: the coating jar is preheated to 38 ℃, spraying, 45 ℃ of coating temperature, atomizing pressure 0.45MPa, spray liquid flow 50ml/min, spraying continues dry 20min after finishing, granulate is got the directly micropill of 400-1000 micron of ball; After testing, aspirin content 82.08%, sundry item meets quality standard.
(3) micropill is directly filled, make aspirin Intestine-soluble micro-pill capsules.
After testing, aspirin content is labelled amount 95-105%, and sundry item meets the capsule quality standard.
Embodiment 3
(1) get the aspirin 80g of 0-300 micron, with 30 POVIDONE K 30 BP/USP 30 2-5g, hypromellose 0.2-0.8g makes 5% alcoholic solution as wetting agent, makes active ball core.Dry.Granulate.Get the aspirin micropill;
(2) get II acrylic resin 3-18g, triethyl citrate 0.5-1.5g, certain herbaceous plants with big flowers diacid fourth diester 0.2-0.5g, Si Ban-60 0.01-0.06g, Pulvis Talci 0.2-0.4g, pure water 5-30g is mixed with solution, carry out coating, the fluidized coating parameter is: the coating jar is preheated to 38 ℃, spraying, 35 ℃ of coating temperature, atomizing pressure 0.35MPa, spray liquid flow 60ml/min, spraying continues dry 20min after finishing, granulate is got the directly micropill of 400-1000 micron of ball; After testing, aspirin content 82.00%, sundry item meets quality standard.
(3) micropill is directly filled, make aspirin Intestine-soluble micro-pill capsules.
After testing, aspirin content is labelled amount 95-105%, and sundry item meets the capsule quality standard.
Embodiment 4
The qualification rate check (27 editions formulations of this canonical reference American Pharmacopeia) of aspirin Intestine-soluble micro-pill capsules
Below be that with preparation method quantity-produced aspirin Intestine-soluble micro-pill three batch samples of the present invention, assay is as follows:
Project standard 080,301 080,302 080303
Character white micropill is up to specification up to specification
Discriminating is positive reaction and is positive reaction and is positive reaction and is positive reaction
Free salicylic acid＜0.3% 0.02% 0.022% 0.018%
In the release acid:＜7% 1.10% 1.12% 1.16%
In the buffer solution: 〉=80% 98.80% 98.55% 99.20%
Content 75%-85% 82.20% 82.81% 82.33%
Microbial limit is up to specification
Sundry item all meets the capsule quality standard.
Claims (6)
1. the preparation method of an aspirin Intestine-soluble micro-pill capsules comprises:
(1) preparation of active medicine ball core
Get the aspirin 50-80g of 0-300 micron, use polyvidone 1-5g, hypromellose 0.1-0.8g, with mass percent concentration be 5% alcoholic solution as wetting agent, make active ball core;
(2) enteric coating
Get coating adjuvant 3-60g, the plasticizer 0.3-6g, releasing agent 0.01-0.06g, Pulvis Talci 0.1-0.5g and the pure water 5-30g that contain the enteric function and be mixed with solution, carry out fluidized coating and drying, parameter is: the fluidized coating jar is preheated to 38 ℃, spraying, 25-55 ℃ of coating temperature, atomizing pressure 0.2-0.45MPa, spray liquid flow 2-80ml/min is after spraying finishes, continue dry 20min, granulate is got the directly micropill of 400-1000 micron of ball, promptly;
(3) micropill is directly filled, be prepared into aspirin Intestine-soluble micro-pill capsules.
2. the preparation method of a kind of aspirin Intestine-soluble micro-pill capsules according to claim 1, it is characterized in that: the coating adjuvant that contains the enteric function in the described step (2) is a polyacrylic resin.
3. the preparation method of a kind of aspirin Intestine-soluble micro-pill capsules according to claim 1, it is characterized in that: the coating adjuvant that contains the enteric function in the described step (2) is II acrylic resin or III acrylic resin.
4. the preparation method of a kind of aspirin Intestine-soluble micro-pill capsules according to claim 1 is characterized in that: the plasticizer in the described step (2) is selected from one or both the mixture in glyceryl monostearate, triethyl citrate, Macrogol 200-20000, certain herbaceous plants with big flowers diacid fourth diester, the diethyl phthalate.
5. the preparation method of a kind of aspirin Intestine-soluble micro-pill capsules according to claim 1 is characterized in that: the releasing agent in the described step (2) is polysorbas20-100 or the 20-100 of class of department.
6. the preparation method of a kind of aspirin Intestine-soluble micro-pill capsules according to claim 1 is characterized in that: the content 75%-85% of aspirin in the described aspirin Intestine-soluble micro-pill.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100458023A CN101491508B (en) | 2009-01-23 | 2009-01-23 | Preparation method of aspirin Intestine-soluble micro-pill capsules |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100458023A CN101491508B (en) | 2009-01-23 | 2009-01-23 | Preparation method of aspirin Intestine-soluble micro-pill capsules |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101491508A CN101491508A (en) | 2009-07-29 |
| CN101491508B true CN101491508B (en) | 2011-04-20 |
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| CN2009100458023A Active CN101491508B (en) | 2009-01-23 | 2009-01-23 | Preparation method of aspirin Intestine-soluble micro-pill capsules |
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| CN104606167B (en) * | 2015-02-11 | 2016-01-13 | 天津力生制药股份有限公司 | A kind of aspirin Intestine-soluble micro-pill capsules and preparation method thereof |
| CN110478333A (en) * | 2019-06-20 | 2019-11-22 | 南京知和医药科技有限公司 | Compound omeprazole capsulae enterosolubilis and preparation method thereof |
| CN110235972A (en) * | 2019-07-23 | 2019-09-17 | 胡江宇 | Ponkan gel candy and its vacuum production method |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020034546A1 (en) * | 1998-03-18 | 2002-03-21 | Ismat Ullah | Pharmaceutical composition containing a combination of a statin and aspirin and method |
| CN1522702A (en) * | 2003-09-08 | 2004-08-25 | 天津太平洋制药有限公司 | Slow and control release aspirin capsule formulation and method for making same |
| CN1554348A (en) * | 2003-12-24 | 2004-12-15 | 天津太平洋制药有限公司 | Method for preparing slow release micro pill of aspirin |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020034546A1 (en) * | 1998-03-18 | 2002-03-21 | Ismat Ullah | Pharmaceutical composition containing a combination of a statin and aspirin and method |
| CN1522702A (en) * | 2003-09-08 | 2004-08-25 | 天津太平洋制药有限公司 | Slow and control release aspirin capsule formulation and method for making same |
| CN1554348A (en) * | 2003-12-24 | 2004-12-15 | 天津太平洋制药有限公司 | Method for preparing slow release micro pill of aspirin |
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