CN111991367A - Esomeprazole magnesium pulse pellet capsule and preparation method thereof - Google Patents
Esomeprazole magnesium pulse pellet capsule and preparation method thereof Download PDFInfo
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- CN111991367A CN111991367A CN202010991585.3A CN202010991585A CN111991367A CN 111991367 A CN111991367 A CN 111991367A CN 202010991585 A CN202010991585 A CN 202010991585A CN 111991367 A CN111991367 A CN 111991367A
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- esomeprazole magnesium
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- 239000008188 pellet Substances 0.000 title claims abstract description 144
- 229960000197 esomeprazole magnesium Drugs 0.000 title claims abstract description 131
- 238000002360 preparation method Methods 0.000 title claims abstract description 35
- 239000002775 capsule Substances 0.000 title claims abstract description 33
- KWORUUGOSLYAGD-WLHYKHABSA-N magnesium;5-methoxy-2-[(r)-(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-ide Chemical compound [Mg+2].C([S@@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C.C([S@@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C KWORUUGOSLYAGD-WLHYKHABSA-N 0.000 title claims abstract 40
- 239000011248 coating agent Substances 0.000 claims abstract description 122
- 238000000576 coating method Methods 0.000 claims abstract description 122
- 239000003814 drug Substances 0.000 claims abstract description 59
- 239000010410 layer Substances 0.000 claims abstract description 58
- 229940079593 drug Drugs 0.000 claims abstract description 47
- 239000012055 enteric layer Substances 0.000 claims abstract description 30
- 238000002955 isolation Methods 0.000 claims abstract description 27
- 239000006187 pill Substances 0.000 claims abstract description 16
- 239000000463 material Substances 0.000 claims description 55
- 238000005507 spraying Methods 0.000 claims description 28
- 239000003795 chemical substances by application Substances 0.000 claims description 25
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 24
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 24
- 239000007788 liquid Substances 0.000 claims description 23
- 238000000889 atomisation Methods 0.000 claims description 20
- 239000004014 plasticizer Substances 0.000 claims description 20
- 239000000454 talc Substances 0.000 claims description 18
- 229910052623 talc Inorganic materials 0.000 claims description 18
- 238000001035 drying Methods 0.000 claims description 16
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical group CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 15
- 239000000843 powder Substances 0.000 claims description 13
- 239000000945 filler Substances 0.000 claims description 11
- 238000002156 mixing Methods 0.000 claims description 11
- 238000007873 sieving Methods 0.000 claims description 11
- 239000003381 stabilizer Substances 0.000 claims description 11
- 229920003139 Eudragit® L 100 Polymers 0.000 claims description 10
- 229920003141 Eudragit® S 100 Polymers 0.000 claims description 10
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 10
- 229930006000 Sucrose Natural products 0.000 claims description 10
- 239000005720 sucrose Substances 0.000 claims description 10
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 9
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 9
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical group [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 9
- 239000001095 magnesium carbonate Substances 0.000 claims description 9
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 9
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 9
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 9
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 8
- 239000007884 disintegrant Substances 0.000 claims description 7
- 239000001069 triethyl citrate Substances 0.000 claims description 6
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 6
- 235000013769 triethyl citrate Nutrition 0.000 claims description 6
- 229920003138 Eudragit® L 30 D-55 Polymers 0.000 claims description 5
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 claims description 5
- 238000011049 filling Methods 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 238000007664 blowing Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 230000002431 foraging effect Effects 0.000 claims 2
- 239000002253 acid Substances 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 6
- 230000027119 gastric acid secretion Effects 0.000 abstract description 6
- 239000008280 blood Substances 0.000 abstract description 3
- 210000004369 blood Anatomy 0.000 abstract description 3
- 230000005764 inhibitory process Effects 0.000 abstract description 3
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- 230000001419 dependent effect Effects 0.000 abstract description 2
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- 230000002035 prolonged effect Effects 0.000 abstract description 2
- 230000033228 biological regulation Effects 0.000 abstract 1
- KWORUUGOSLYAGD-YPPDDXJESA-N esomeprazole magnesium Chemical compound [Mg+2].C([S@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C.C([S@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C KWORUUGOSLYAGD-YPPDDXJESA-N 0.000 description 93
- 239000000243 solution Substances 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000007921 spray Substances 0.000 description 10
- 239000012153 distilled water Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 6
- 238000010008 shearing Methods 0.000 description 6
- 230000001186 cumulative effect Effects 0.000 description 5
- 239000002662 enteric coated tablet Substances 0.000 description 5
- 239000000853 adhesive Substances 0.000 description 4
- 230000001070 adhesive effect Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 210000004211 gastric acid Anatomy 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 229960004770 esomeprazole Drugs 0.000 description 3
- SUBDBMMJDZJVOS-DEOSSOPVSA-N esomeprazole Chemical compound C([S@](=O)C1=NC2=CC=C(C=C2N1)OC)C1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-DEOSSOPVSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 229960001708 magnesium carbonate Drugs 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 229960004793 sucrose Drugs 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- -1 5-methoxy-2- [ (S) - [ (4-methoxy-3, 5-dimethyl-2-pyridyl) methyl ] sulfinyl ] -1H-benzimidazol-1-yl Chemical group 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- 206010019375 Helicobacter infections Diseases 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 239000009147 Kangxin Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 235000021152 breakfast Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
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- 230000000052 comparative effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
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- 238000005516 engineering process Methods 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
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- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- QWDJLDTYWNBUKE-UHFFFAOYSA-L magnesium bicarbonate Chemical compound [Mg+2].OC([O-])=O.OC([O-])=O QWDJLDTYWNBUKE-UHFFFAOYSA-L 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
- 210000001711 oxyntic cell Anatomy 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000001020 rhythmical effect Effects 0.000 description 1
- 238000005563 spheronization Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an esomeprazole magnesium pulse pellet capsule and a preparation method thereof. The esomeprazole magnesium pulse pellet capsule is internally composed of two different pH-dependent enteric pellets, wherein the enteric pellet I is prepared by sequentially coating an esomeprazole magnesium drug-containing pellet core with an isolation layer I and an enteric layer I; the enteric-coated pellet II is prepared by sequentially coating an isolation layer II and an enteric-coated layer II outside an esomeprazole magnesium drug-containing pellet core. The invention has the advantages that: aiming at the rhythmicity of gastric acid secretion time, according to the chronodynamics principle, a micro-pill for releasing the drug by two pulses is designed, and the micro-pill is administrated once a day to maintain good acid inhibition effect at night; the medicine is released in the intestinal tract by two times of pulses, so that the retention time of the medicine is prolonged, and the bioavailability is improved; the pulse preparation is prepared in the form of pellets, and has low cost, flexible regulation of drug release behavior and small fluctuation of blood concentration.
Description
Technical Field
The invention relates to an esomeprazole magnesium pulse capsule and a preparation method thereof, belonging to the technical field of medicines.
Background
Esomeprazole magnesium trihydrate, the english name: esomeprazole magnesium trihydrate, chemical name: magnesium bis (5-methoxy-2- [ (S) - [ (4-methoxy-3, 5-dimethyl-2-pyridyl) methyl ] sulfinyl ] -1H-benzimidazol-1-yl) salt trihydrate. The physicochemical property of the material is stable under the alkalescent condition and is easy to degrade in the acid environment. Molecular weight: 767.2, chemical structural formula:
esomeprazole magnesium is the S-isomer of omeprazole, which inhibits gastric acid secretion by specifically targeting parietal cells of the stomach and activating to active achiral sulfenamides in combination with H +/K + -atpase. It is suitable for symptom control and long-term treatment of gastroesophageal reflux disease; eradication of helicobacter pylori in combination with appropriate antibacterial therapy and healing of duodenal ulcers associated with helicobacter pylori infection; gastric ulcer diseases associated with nonsteroidal anti-inflammatory drug therapy.
The esomeprazole magnesium is a second-generation proton pump inhibitor, has the characteristics of high safety, quick response and long action time, and is widely applied clinically. The esomeprazole magnesium is degraded in acidic and neutral media, and is degraded particularly rapidly in an acidic environment. Therefore, as an oral medicine, the damage of gastric acid is obvious, most of the related preparations on the market adopt a protection means to prevent esomeprazole magnesium from directly contacting with gastric juice, for example, the esomeprazole magnesium is prepared into a pellet preparation, the medicine is dispersed in a plurality of pellets, and the release position and time are controlled by a membrane control technology. Chinese patent CN104546787A discloses an esomeprazole magnesium enteric-coated tablet containing esomeprazole magnesium pellets and a preparation method thereof, wherein the enteric-coated tablet is prepared by isostatically pressing the pellets taking esomeprazole magnesium as an active ingredient, a diluent, a disintegrating agent, a lubricant and the like; the Chinese invention patent CN102100671A discloses an esomeprazole magnesium enteric-coated pellet and a preparation method thereof, wherein an active pellet core of the enteric-coated pellet consists of esomeprazole magnesium and other medicinal excipients, and the enteric-coated pellet is finally prepared by coating an isolation layer and an enteric layer by layer. The Chinese invention patent CN102670521A discloses an esomeprazole magnesium enteric-coated pellet and a preparation method thereof, wherein pH values of the enteric-coated pellet are respectively adjusted by using an acid-base regulator in a drug-containing layer and an isolating layer, so that the stability of esomeprazole magnesium is enhanced.
The technical scheme solves the problem of controlling the release of esomeprazole magnesium in vivo, but chronopharmacological research shows that the physiological function of a human body and the attack time of a plurality of diseases have the characteristic of obvious periodic change, the gastric acid secretion of a human has the similar characteristic, the physiological function and the attack time of a plurality of diseases slowly rise from the midday to about 20 hours, the gastric acid secretion reaches a peak value at 22 hours, the gastric acid secretion is maintained at a higher level at night, and the administration of the esomeprazole magnesium is generally recommended to be carried out once before breakfast and before sleep to ensure the acid inhibition effect. However, the current esomeprazole magnesium pellet preparation cannot release the gastric acid in a rhythmic manner, so that the phenomenon of acid breakthrough occurs in the night of a patient.
Disclosure of Invention
The invention aims to provide an esomeprazole magnesium pulse pellet capsule and a preparation method thereof, and the esomeprazole magnesium pulse pellet capsule is combined with the advantages of a pulse preparation and a multi-unit drug delivery system, aims at the biorhythmic release of drugs of gastric acid, is favorable for improving the effect of inhibiting gastric acid secretion, and reduces the occurrence of acid breakthrough phenomenon at night.
In order to achieve the technical purpose, the technical scheme adopted by the invention is as follows:
an esomeprazole magnesium pulse pellet capsule comprises an active drug esomeprazole magnesium and other pharmaceutically acceptable auxiliary materials. The esomeprazole magnesium medicine consists of esomeprazole magnesium enteric-coated pellets I and esomeprazole magnesium enteric-coated pellets II which are different in pH dependence, wherein the mass ratio of the esomeprazole magnesium in the two pellets is 1: 3.
the esomeprazole magnesium enteric-coated pellets I and II consist of drug-containing pellet cores, isolating layers and enteric-coated layers.
The drug-containing pill core is prepared by wrapping esomeprazole magnesium outside a blank drug core, a filling agent, a stabilizing agent and a disintegrating agent, and comprises the following components in parts by weight: 1500 parts of blank pill core, 200 parts of esomeprazole magnesium, 500 parts of filler, 80 parts of stabilizer and 24 parts of disintegrant; wherein the filler is formed by mixing microcrystalline cellulose and sucrose, the stabilizer is magnesium carbonate, and the disintegrant is low-substituted hydroxypropyl cellulose.
In the esomeprazole magnesium enteric-coated pellet I, the isolating layer I consists of a coating material HPMC, and the coating weight is increased by 8%; the enteric layer I consists of a coating material, a plasticizer and an anti-sticking agent, and the weight parts of the enteric layer I are as follows: 100 parts of coating material (solid), 10 parts of plasticizer and 50 parts of anti-sticking agent, wherein the solid content is 20 percent, the coating material in the enteric-coated layer I is L30D-55, the plasticizer is triethyl citrate, and the anti-sticking agent is talc.
In the esomeprazole magnesium enteric-coated pellet II, the isolating layer II consists of a coating material HPMC, and the weight of the coating is increased by 5%; the enteric coating layer II comprises a coating material, a plasticizer and an anti-sticking agent, and the weight parts of the enteric coating layer II are as follows: 100 parts of coating material, 10 parts of plasticizer, 50 parts of anti-sticking agent and 10% of solid content. Wherein the coating material in the enteric layer II consists of Eudragit L100 and Eudragit S100, and the weight ratio is 1: 3; the plasticizer is triethyl citrate and the antisticking agent is talc.
The preparation method of the esomeprazole magnesium pulse pellet comprises the steps of preparing an esomeprazole magnesium drug-containing pellet core, wherein the enteric-coated pellet I is prepared by sequentially coating an isolating layer I and an enteric-coated layer I outside the esomeprazole magnesium drug-containing pellet core; the enteric-coated pellet II is prepared by sequentially coating an isolation layer II and an enteric-coated layer II outside an esomeprazole magnesium drug-containing pellet core.
Wherein the preparation of the esomeprazole magnesium drug-containing pill core comprises the following steps:
respectively sieving esomeprazole magnesium, a filling agent, a disintegrating agent and a stabilizing agent through a 80-mesh sieve, equivalently and gradually mixing, loading by adopting a centrifugal method, gradually layering powder on the surface of a blank pill core under the action of an adhesive, and drying in an oven after loading; the weight portion ratio is as follows: 1500 parts of blank pill core, 200 parts of esomeprazole magnesium, 500 parts of filler, 80 parts of stabilizer and 24 parts of disintegrant. The blank pellet core is a sucrose pellet core; the filler is microcrystalline cellulose: sucrose =3:7 mixture; the stabilizer is magnesium carbonate; the disintegrant is low-substituted hydroxypropyl cellulose; the binder was a 3% HPMC aqueous solution.
In the preparation method, the material powder is added into a centrifugal pill making machine for powder layering and medicine application, the rotating speed of a wheel disc is 200rpm, the liquid spraying speed is 3.5mL/min, and the spheronization time is 3 min.
The preparation of the enteric-coated pellet I comprises the following steps:
(1) coating of an isolation layer I: preparing 5% HPMC E5 water solution, placing the prepared esomeprazole magnesium drug-containing pellet core in a fluidized bed, and performing fluidized coating and drying on the coating solution of the isolation layer I, wherein the weight of the isolation layer I is increased by 8%.
(2) Coating of the enteric-coated pellet I: the enteric layer adopts Eudragit L30D-55 as a coating material, and a plasticizer and an anti-sticking agent are added and mixed in a coating solvent, the product obtained in the step (1) is subjected to fluidized coating and drying, and is aged in an oven, wherein the weight ratio is as follows: 100 parts of coating material (solid), 10 parts of plasticizer and 50 parts of anti-sticking agent, and the solid content is 20%. The plasticizer is triethyl citrate; the antisticking agent is talc.
In the preparation method, the coating parameter of the fluidized bed in the step (1) is the material temperature of 30-35 ℃; the atomization pressure is 0.1 MPa; the rotating speed of the fan is 800-1200 rpm; the spraying speed is 2.7 mL/min.
In the preparation method, the coating parameter of the fluidized bed in the step (2) is the material temperature of 30-35 ℃; the atomization pressure is 0.1 MPa; the rotating speed of the fan is 800-1200 rpm; the spraying speed is 2.7 mL/min.
The preparation of the enteric-coated pellet II comprises the following steps:
(1) and (3) coating of an isolation layer II: preparing 5% HPMC E5 water solution, placing the prepared esomeprazole magnesium drug-containing pellet core in a fluidized bed, and performing fluidized coating and drying on the coating solution of the isolation layer II, wherein the weight of the isolation layer II is increased by 5%.
(2) Coating of an enteric pellet II: the enteric layer adopts Eudragit L100 and Eudragit S100 (1: 3) as coating materials, and adds plasticizer and antisticking agent to mix in coating solvent, and fluidizes and coats the product of the step (1) and dries, and the baking oven ages, wherein the weight ratio is: 100 parts of coating material, 10 parts of plasticizer, 50 parts of anti-sticking agent, 95% ethanol as solvent and 10% of solid content. The plasticizer is triethyl citrate; the antisticking agent is talc.
In the preparation method, the coating parameter of the fluidized bed in the step (1) is the material temperature of 30-35 ℃; the atomization pressure is 0.1 MPa; the rotating speed of the fan is 1000-1400 rpm; the spraying speed is 2.7 mL/min.
In the preparation method, the fluidized bed coating parameter in the step (2) is the material temperature of 25-30 ℃; the atomization pressure is 0.1-0.12 MPa; the rotating speed of the fan is 800-1300 rpm; the spraying speed is 4.4-6.6 mL/min.
Wherein the preparation of the esomeprazole magnesium pulse pellet comprises the following steps:
and respectively measuring the drug content of the enteric-coated pellet I and the drug content of the enteric-coated pellet II, and filling the enteric-coated pellet I and the enteric-coated pellet II into the same capsule shell according to the proportion of the specification dose of 1:3 to obtain the esomeprazole magnesium pulse pellet capsule.
The invention has the advantages that the preparation of different pH-dependent esomeprazole magnesium enteric-coated pellets leads the drug to be released in the intestinal tract by two times of pulse, prolongs the retention time of the drug and improves the bioavailability.
The pulse micro-pill prepared from esomeprazole magnesium can design a drug delivery scheme according to the chronopharmacology principle, so that the Tmax in a drug body coincides with the active peak period of gastric acid at night, and a good acid inhibition effect is ensured at night.
The pellet is used as a carrier of a multi-pulse preparation, so that the cost is low and the preparation process is simple; the pill type drug release is adopted, the behavior adjustment is flexible, the blood concentration fluctuation is small, and the side effect is lower.
Drawings
FIG. 1 is a graph comparing the in vitro cumulative release versus time curves for the product of example 4.
Figure 2 is a graph comparing the plasma concentration-time profiles of the product of example 4.
Detailed Description
The following is a further description with reference to specific examples.
Example 1
(1) Preparing an esomeprazole magnesium drug-containing pellet core:
prescription:
| blank pill core | 75.0 g |
| Esomeprazole magnesium | 10.0 g (in Esomeprazole) |
| Microcrystalline cellulose | 7.5 g |
| Sucrose | 17.5 g |
| Magnesium carbonate | 4.0 g |
| Low-substituted hydroxypropyl cellulose | 1.2 g |
| 3% HPMC E5 aqueous solution | 20 mL |
The esomeprazole magnesium, microcrystalline cellulose, sucrose, magnesium carbonate and low-substituted hydroxypropyl cellulose in the prescription amount are respectively sieved by a sieve of 80 meshes, and then are added in equal amount and mixed uniformly. Placing a blank pellet core in a centrifugal granulator, operating the machine after setting process parameters, wherein the parameters are that the rotation speed of a wheel disc is 200rpm, the blast frequency is 25 Hz, the spray pressure is 0.16Mpa and the spray speed is 3.5mL/min, setting the position of a baffle plate to enable the blank pellet core to move in a rope shape and have the maximum operation shape in a sector, adjusting the position of a spray gun to enable the spray gun head to correspond to the center position of the sector, slowly adding powder which is uniformly mixed with medicines and auxiliary materials from a feeding port while spraying an adhesive, gradually layering the powder on the surface of the blank pellet core, rounding for 3min after powder feeding is completed, transferring the blank pellet core to an oven for drying at 40 ℃ for 1h, sieving, bagging and sealing, and storing.
(2) Preparing esomeprazole magnesium enteric-coated pellets I:
an isolation layer I: 5% HPMC E5 water solution is prepared as coating solution of the isolating layer for coating. HPMC E5 was slowly added to hot distilled water under stirring and allowed to cool for use. Placing the esomeprazole magnesium drug-containing pellet core prepared by 1/4 in a fluidized bed, coating with the isolation layer I, wherein the weight of the coating is increased by 8%. Controlling the temperature of the material to be 30-35 ℃; the atomization pressure is 0.1 MPa; the liquid spraying speed is 2.7 mL/min; the rotating speed of the fan is 800 rpm; drying in fluidized bed for 30min after coating.
Coating an enteric layer I:
prescription:
| Eudragit L30D-55 | 24.59 g |
| citric acid triethyl ester | 0.74 g |
| Talc | 3.69 |
| Distilled water | |
| 30 mL |
Adding TEC and talc into purified water, high shearing at the rotation speed of 5000 rpm for 10 min, slowly adding into the L30D-55 dispersion liquid, mixing for 30min by a stirrer, and sieving with a 80-mesh sieve to obtain the enteric-coated layer I coating liquid. And (3) placing the esomeprazole magnesium pellets coated with the isolating layer I into a fluidized bed, coating the enteric layer I, and increasing the weight of the coating by 30%. Controlling the temperature of the material to be 30-35 ℃; the atomization pressure is 0.1 MPa; the liquid spraying speed is 2.7 mL/min; the rotating speed of the fan is 800 rpm; after coating, the film was transferred to an oven and aged at 40 ℃ for 2 h.
(3) Preparing esomeprazole magnesium enteric-coated pellets II:
and (3) coating an isolation layer II:
5% HPMC E5 water solution is prepared as coating solution of the isolating layer for coating. HPMC E5 was slowly added to hot distilled water under stirring and allowed to cool for use. And (3) placing the esomeprazole magnesium drug-containing pellet core prepared by 3/4 into a fluidized bed to coat the layer II, wherein the weight of the coating is increased by 5%. Controlling the temperature of the material to be 30-35 ℃; the atomization pressure is 0.1 MPa; the liquid spraying speed is 2.7 mL/min; the rotating speed of the fan is 1000 rpm; drying in fluidized bed for 30min after coating.
Coating an enteric layer II:
prescription:
| Eudragit L100 | 9.84 g |
| Eudragit S100 | 29.53 g |
| citric acid triethyl ester | 3.94 g |
| Talc | 19.69 g |
| 95% ethanol | 700 mL |
Dissolving the mixed coating material of Eudragit L100 and Eudragit S100 in 95% ethanol with the volume of 50%, stirring for 3 h, then adding TEC and talc into the 95% ethanol with the remaining volume of 50%, high-shearing at the rotation speed of 5000 rpm for 10 min, adding the auxiliary material suspension into the Utex solution, mixing for 30min by a stirrer, and sieving with a 80-mesh sieve to obtain the coating solution of the enteric layer II. And (3) placing the esomeprazole magnesium pellets coated with the isolation layer II into a fluidized bed, coating the enteric layer II, and increasing the weight of the coating by 60%. Controlling the temperature of the material to be 25-30 ℃; the atomization pressure is 0.1-0.12 MPa; the liquid spraying speed is 6.6 mL/min; the rotating speed of the fan is 800-1000 rpm; after coating, the film was transferred to an oven and aged at 40 ℃ for 2 h.
(4) Preparation of esomeprazole magnesium pulse pellet capsule
Weighing the esomeprazole magnesium enteric-coated pellet I and the esomeprazole magnesium enteric-coated pellet II, and filling the pellet I and the pellet II which are equivalent to the esomeprazole magnesium 1/4 and 3/4 in the capsule shell to obtain the esomeprazole magnesium pulse pellet capsule.
Example 2
(1) Preparing an esomeprazole magnesium drug-containing pellet core:
prescription:
| blank pill core | 150.0 g |
| Esomeprazole magnesium | 20.0 g (in Esomeprazole) |
| Microcrystalline cellulose | 15.0 g |
| Sucrose | 35.0 g |
| Magnesium carbonate | 8.0 g |
| Low-substituted hydroxypropyl cellulose | 2.4 g |
| 3% HPMC E5 |
30 mL |
The esomeprazole magnesium, microcrystalline cellulose, sucrose, magnesium carbonate and low-substituted hydroxypropyl cellulose in the prescription amount are respectively sieved by a sieve of 80 meshes, and then are added in equal amount and mixed uniformly. Placing a blank pellet core in a centrifugal granulator, operating the machine after setting process parameters, wherein the parameters are that the rotation speed of a wheel disc is 200rpm, the blast frequency is 25 Hz, the spray pressure is 0.16Mpa and the spray speed is 3.5mL/min, setting the position of a baffle plate to enable the blank pellet core to move in a rope shape and have the maximum operation shape in a sector, adjusting the position of a spray gun to enable the spray gun head to correspond to the center position of the sector, slowly adding powder which is uniformly mixed with medicines and auxiliary materials from a feeding port while spraying an adhesive, gradually layering the powder on the surface of the blank pellet core, rounding for 3min after powder feeding is completed, transferring the blank pellet core to an oven for drying at 40 ℃ for 1h, sieving, bagging and sealing, and storing.
(2) Preparing esomeprazole magnesium enteric-coated pellets I:
an isolation layer I: 5% HPMC E5 water solution is prepared as coating solution of the isolating layer for coating. HPMC E5 was slowly added to hot distilled water under stirring and allowed to cool for use. Placing the esomeprazole magnesium drug-containing pellet core prepared by 1/4 in a fluidized bed, coating with the isolation layer I, wherein the weight of the coating is increased by 8%. Controlling the temperature of the material to be 30-35 ℃; the atomization pressure is 0.1 MPa; the liquid spraying speed is 2.7 mL/min; the rotating speed of the fan is 1000 rpm; drying in fluidized bed for 30min after coating.
Coating an enteric layer I: prescription:
| Eudragit L30D-55 | 49.19 g |
| citric acid triethyl ester | 1.48 g |
| Talc | 7.38 |
| Distilled water | |
| 60 mL |
Adding TEC and talc into purified water, high shearing at the rotation speed of 5000 rpm for 10 min, slowly adding into the L30D-55 dispersion liquid, mixing for 30min by a stirrer, and sieving with a 80-mesh sieve to obtain the enteric-coated layer I coating liquid. And (3) placing the esomeprazole magnesium pellets coated with the isolating layer I into a fluidized bed, coating the enteric layer I, and increasing the weight of the coating by 30%. Controlling the temperature of the material to be 30-35 ℃; the atomization pressure is 0.1 MPa; the liquid spraying speed is 2.7 mL/min; the rotating speed of the fan is 800-1000 rpm; after coating, the film was transferred to an oven and aged at 40 ℃ for 2 h.
(3) Preparing esomeprazole magnesium enteric-coated pellets II:
and (3) coating an isolation layer II:
5% HPMC E5 water solution is prepared as coating solution of the isolating layer for coating. HPMC E5 was slowly added to hot distilled water under stirring and allowed to cool for use. And (3) placing the esomeprazole magnesium drug-containing pellet core prepared by 3/4 into a fluidized bed to coat the layer II, wherein the weight of the coating is increased by 5%. Controlling the temperature of the material to be 30-35 ℃; the atomization pressure is 0.1 MPa; the liquid spraying speed is 2.7 mL/min; the rotating speed of the fan is 1200 rpm; drying in fluidized bed for 30min after coating.
Coating an enteric layer II:
prescription:
| Eudragit L100 | 19.69 g |
| Eudragit S100 | 59.06 g |
| citric acid triethyl ester | 7.88 g |
| Talc | 39.38 g |
| 95% ethanol | 1400 mL |
Dissolving the mixed coating material of Eudragit L100 and Eudragit S100 in 95% ethanol with the volume of 50%, stirring for 3 h, then adding TEC and talc into the 95% ethanol with the remaining volume of 50%, high-shearing at the rotation speed of 5000 rpm for 10 min, adding the auxiliary material suspension into the Utex solution, mixing for 30min by a stirrer, and sieving with a 80-mesh sieve to obtain the coating solution of the enteric layer II. And (3) placing the esomeprazole magnesium pellets coated with the isolation layer II into a fluidized bed, coating the enteric layer II, and increasing the weight of the coating by 60%. Controlling the temperature of the material to be 25-30 ℃; the atomization pressure is 0.1-0.12 MPa; the liquid spraying speed is 6.6 mL/min; the rotating speed of the fan is 1000-1200 rpm; after coating, the film was transferred to an oven and aged at 40 ℃ for 2 h.
(4) Preparation of esomeprazole magnesium pulse pellet capsule
Weighing the esomeprazole magnesium enteric-coated pellet I and the esomeprazole magnesium enteric-coated pellet II, and filling the pellet I and the pellet II which are equivalent to the esomeprazole magnesium 1/4 and 3/4 in the capsule shell to obtain the esomeprazole magnesium pulse pellet capsule.
Example 3
(1) Preparing an esomeprazole magnesium drug-containing pellet core:
prescription:
| blank pill core | 300.0 g |
| Esomeprazole magnesium | 40.0 g (in Esomeprazole) |
| Microcrystalline cellulose | 30.0 g |
| Sucrose | 70.0 g |
| Magnesium carbonate | 16.0 g |
| Low-substituted hydroxypropyl cellulose | 4.8 g |
| 3% HPMC E5 aqueous solution | 50 mL |
The esomeprazole magnesium, microcrystalline cellulose, sucrose, magnesium carbonate and low-substituted hydroxypropyl cellulose in the prescription amount are respectively sieved by a sieve of 80 meshes, and then are added in equal amount and mixed uniformly. Placing a blank pellet core in a centrifugal granulator, operating the machine after setting process parameters, wherein the parameters are that the rotation speed of a wheel disc is 200rpm, the blowing frequency is 30Hz, the spraying pressure is 0.16Mpa and the spraying speed is 3.5mL/min, setting the position of a baffle plate to enable the blank pellet core to move in a rope shape and have the maximum operation shape in a sector, adjusting the position of a spray gun to enable the spray gun head to correspond to the center position of the sector, slowly adding powder which is uniformly mixed with medicines and auxiliary materials from a feeding port while spraying an adhesive, gradually layering the powder on the surface of the blank pellet core, rounding for 3min after powder feeding is completed, transferring the blank pellet core to an oven for drying at 40 ℃ for 1h, sieving, bagging and sealing, and storing.
(2) Preparing esomeprazole magnesium enteric-coated pellets I:
an isolation layer I: 5% HPMC E5 water solution is prepared as coating solution of the isolating layer for coating. HPMC E5 was slowly added to hot distilled water under stirring and allowed to cool for use. The prepared esomeprazole magnesium drug-containing pellet core is placed in a fluidized bed to coat the isolation layer I, and the weight of the coating is increased by 8%. Controlling the temperature of the material to be 30-35 ℃; the atomization pressure is 0.1 MPa; the liquid spraying speed is 2.7 mL/min; the rotating speed of the fan is 1200 rpm; drying in fluidized bed for 30min after coating.
Coating an enteric layer I: prescription:
| Eudragit L30D-55 | 81.98 g |
| citric acid triethyl ester | 2.46 g |
| Talc | 12.30 |
| Distilled water | |
| 100 mL |
Adding TEC and talc into purified water, high shearing at the rotation speed of 5000 rpm for 10 min, slowly adding into the L30D-55 dispersion liquid, mixing for 30min by a stirrer, and sieving with a 80-mesh sieve to obtain the enteric-coated layer I coating liquid. And (3) placing the esomeprazole magnesium pellets coated with the isolating layer I into a fluidized bed, coating the enteric layer I, and increasing the weight of the coating by 30%. Controlling the temperature of the material to be 30-35 ℃; the atomization pressure is 0.1 MPa; the liquid spraying speed is 2.7 mL/min; the rotating speed of the fan is 1000-1200 rpm; after coating, the film was transferred to an oven and aged at 40 ℃ for 2 h.
(3) Preparing esomeprazole magnesium enteric-coated pellets II:
and (3) coating an isolation layer II:
5% HPMC E5 water solution is prepared as coating solution of the isolating layer for coating. HPMC E5 was slowly added to hot distilled water under stirring and allowed to cool for use. And (3) placing the prepared esomeprazole magnesium drug-containing pellet core into a fluidized bed to coat the layer II, wherein the weight of the coating is increased by 5%. Controlling the temperature of the material to be 30-35 ℃; the atomization pressure is 0.1 MPa; the liquid spraying speed is 2.7 mL/min; the rotating speed of the fan is 1400 rpm; drying in fluidized bed for 30min after coating.
Coating an enteric layer II:
prescription:
| Eudragit L100 | 36.56 g |
| Eudragit S100 | 109.69 g |
| citric acid triethyl ester | 14.63 g |
| Talc | 73.12 g |
| 95% ethanol | 2600 mL |
Dissolving the mixed coating material of Eudragit L100 and Eudragit S100 in 95% ethanol with the volume of 50%, stirring for 3 h, then adding TEC and talc into the 95% ethanol with the remaining volume of 50%, high-shearing at the rotation speed of 5000 rpm for 10 min, adding the auxiliary material suspension into the Utex solution, mixing for 30min by a stirrer, and sieving with a 80-mesh sieve to obtain the coating solution of the enteric layer II. And (3) placing the esomeprazole magnesium pellets coated with the isolation layer II into a fluidized bed, coating the enteric layer II, and increasing the weight of the coating by 60%. Controlling the temperature of the material to be 25-30 ℃; the atomization pressure is 0.1-0.12 MPa; the liquid spraying speed is 6.6 mL/min; the rotating speed of the fan is 1200-1500 rpm; after coating, the film was transferred to an oven and aged at 40 ℃ for 2 h.
(4) Preparation of esomeprazole magnesium pulse pellet capsule
Weighing the esomeprazole magnesium enteric-coated pellet I and the esomeprazole magnesium enteric-coated pellet II, and filling the pellet I and the pellet II which are equivalent to the esomeprazole magnesium 1/4 and 3/4 in the capsule shell to obtain the esomeprazole magnesium pulse pellet capsule.
Example 4: comparative examples
The esomeprazole magnesium pulse pellet capsule obtained in example 2 was subjected to in vitro and in vivo release degree detection and compared with commercially available esomeprazole magnesium enteric-coated tablets (pellet tablets), and the in vitro release curve is shown in fig. 1. As can be seen from figure 1, the 20min cumulative release percentage of the commercially available esomeprazole magnesium enteric-coated tablet (pellet tablet) reaches more than 85%, and 30min almost complete release; and the 20-min cumulative release degree of the esomeprazole magnesium pulse pellet is not less than 20%, the 50-min cumulative release degree is not more than 35%, and the 105-min cumulative release degree is not less than 85%, which shows that the esomeprazole magnesium pulse pellet has obvious two-time pulse effect, the enteric pellet I and the enteric pellet II are completely released, and the enteric pellet II has no burst release phenomenon.
An in vivo drug-time curve is shown, for example, in figure 2, where the pharmacokinetic parameters are as follows:
| major pharmacokinetic parameters | Test group | Control group |
| Time to peak Tmax(h) | 2.00；6.00 | 1.50 |
| Blood drug peak concentration Cmax(mg/L) | 1.79；3.35 | 3.47 |
| Area under the drug-time curve0-24h(mg/L*h) | 25.24 | 20.54 |
| Area under drug-time Curve AUC0-∞(mg/L*h) | 29.28 | 25.36 |
| Average residence time0-24h(h) | 8.70 | 7.57 |
As can be seen from FIG. 2, the commercially available esomeprazole magnesium enteric-coated tablet (pellet tablet) shows a unimodal curve in rats, and the peak time is 1.5 h; the pulse micropill shows obvious double peak curve, the peak reaching time of two times is 2.00 h and 6.00 h respectively, and has obvious pulse medicine releasing characteristic.
The test group compartment model result and the control group compartment model result both accord with a two-chamber model, and the weight coefficients are both 1/cc; the control group only has one-time rapid drug release behavior in vivo, while the preparation of the test group can release the drug in vivo twice, so that the retention time of the drug in vivo is prolonged, and compared with the preparation (KANGXIN) in the market, the pulse preparation has the relative bioavailability of 122 percent and is beneficial to clinical treatment.
Claims (10)
1. An esomeprazole magnesium pulse pellet capsule consists of an active drug esomeprazole magnesium and other pharmaceutically acceptable auxiliary materials; the esomeprazole magnesium enteric-coated pellet is characterized by comprising an esomeprazole magnesium enteric-coated pellet I and an esomeprazole magnesium enteric-coated pellet II, wherein the mass ratio of esomeprazole magnesium is 1: 3.
2. the esomeprazole magnesium pulse pellet capsule according to claim 1, wherein the esomeprazole magnesium enteric pellet I and pellet II consist of drug-containing pellet cores, isolation layers and enteric layers.
3. The esomeprazole magnesium pulse pellet capsule according to claim 1 or 2, wherein the drug-containing pellet core is composed of a blank drug core coated with esomeprazole magnesium, a filler, a stabilizer and a disintegrant, and comprises the following components in parts by weight: 1500 parts of blank pill core, 200 parts of esomeprazole magnesium, 500 parts of filler, 80 parts of stabilizer and 24 parts of disintegrant.
4. The esomeprazole magnesium pulse pellet capsule according to claim 1 or 2, wherein the filler in the drug-containing pellet core is formed by mixing microcrystalline cellulose and sucrose, the stabilizer is magnesium carbonate, and the disintegrant is low-substituted hydroxypropyl cellulose.
5. The esomeprazole magnesium pulse pellet capsule according to claim 1 or 2, wherein in the esomeprazole magnesium enteric pellet I, the isolation layer I consists of a coating material HPMC; the enteric layer I consists of a coating material, a plasticizer and an anti-sticking agent, and the weight parts of the enteric layer I are as follows: 100 parts of coating material, 10 parts of plasticizer, 50 parts of anti-sticking agent and 20% of solid content.
6. The esomeprazole magnesium pulse pellet capsule of claim 1 or 2, wherein the coating material in the enteric layer i is L30D-55, the plasticizer is triethyl citrate, and the anti-sticking agent is talc.
7. The esomeprazole magnesium pulse pellet capsule according to claim 1 or 2, wherein in the esomeprazole magnesium enteric pellet II, the isolation layer II consists of a coating material HPMC; the enteric layer II consists of a coating material, a plasticizer and an anti-sticking agent, and comprises the following components in parts by weight: 100 parts of coating material, 10 parts of plasticizer, 50 parts of anti-sticking agent and 10% of solid content.
8. The esomeprazole magnesium pulse pellet capsule of claim 1 or 2, wherein the coating material in the enteric layer ii consists of Eudragit L100 and Eudragit S100 in a weight ratio of 1: 3; the plasticizer is triethyl citrate and the antisticking agent is talc.
9. The preparation method of the esomeprazole magnesium pulse pellet capsule of claim 1, characterized by comprising the steps of:
(1) preparing an esomeprazole magnesium drug-containing pellet core: respectively sieving esomeprazole magnesium, a filling agent, a disintegrating agent and a stabilizing agent through a 80-mesh sieve, adding and uniformly mixing the esomeprazole magnesium, the filling agent, the disintegrating agent and the stabilizing agent in equal quantity, performing powder layering by adopting a centrifugal method to perform medicine application to prepare an esomeprazole magnesium medicine-containing pill core, and drying the medicine-containing pill core in an oven after the medicine application is completed;
(2) coating of an isolation layer I: preparing 5% HPMC solution as coating solution of the isolating layer I, performing fluidized bed coating on the esomeprazole magnesium drug-containing pellet core prepared in the step (1), and drying, wherein the weight of the coating is increased by 8%;
(3) preparing esomeprazole magnesium enteric-coated pellets I: the enteric layer I selects Eudragit L30D-55 as a coating material, and adds a plasticizer and an anti-sticking agent to be mixed in a coating solvent, the product obtained in the step (2) is subjected to fluidized bed coating, and the product is transferred to an oven for aging;
(4) and (3) coating of an isolation layer II: preparing 5% HPMC solution as coating solution of the isolating layer II, performing fluidized bed coating on the esomeprazole magnesium drug-containing pellet core prepared in the step (1), and drying, wherein the weight of the coating is increased by 5%;
(5) preparing esomeprazole magnesium enteric-coated pellets II: the enteric layer I is prepared by selecting a mixture of Eudragit L100 and Eudragit S100 in a mass ratio of 1:3 as a coating material, adding a plasticizer and an anti-sticking agent, mixing in a coating solvent, coating the product obtained in the step (4) by a fluidized bed, and transferring to an oven for aging;
(6) the preparation method of the esomeprazole magnesium pulse pellet capsule comprises the following steps: and (4) measuring the content of the esomeprazole magnesium enteric-coated pellets I and the esomeprazole magnesium enteric-coated pellets II prepared in the steps (3) and (5), and filling the esomeprazole magnesium enteric-coated pellets I and the esomeprazole magnesium enteric-coated pellets II into capsule shells according to the mass ratio of 1:3 of the esomeprazole magnesium, so as to obtain the esomeprazole magnesium pulse pellet capsule.
10. The preparation method of esomeprazole magnesium pulse pellet capsule according to claim 1 or 9, wherein,
the centrifugal medicine feeding parameter in the step (1) is the rotating speed of a wheel disc of 200 rpm; the liquid spraying speed is 3.5 mL/min; the spraying pressure is 0.16 MPa; the blowing frequency is 25-30 Hz; rounding for 3 min;
the fluidized coating parameter in the step (2) is the material temperature of 30-35 ℃; the atomization pressure is 0.1 MPa; the rotating speed of the fan is 800-1200 rpm; the liquid spraying speed is 2.7 mL/min;
the fluidized coating parameter in the step (3) is material temperature of 30-35 ℃; the atomization pressure is 0.1 MPa; the rotating speed of the fan is 800-1200 rpm; the liquid spraying speed is 2.7 mL/min;
the fluidized coating parameter in the step (4) is the material temperature of 30-35 ℃; the atomization pressure is 0.1 MPa; the rotating speed of the fan is 800-1400 rpm; the liquid spraying speed is 2.7 mL/min;
the fluidized coating parameter in the step (5) is the material temperature of 25-30 ℃; the atomization pressure is 0.1-0.12 MPa; the rotating speed of the fan is 800-1500 rpm; the spraying speed is 4.4-6.6 mL/min.
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| US20080095853A1 (en) * | 2004-11-04 | 2008-04-24 | Niclas Clemmensen | Modified Release For Proton Pump Inhibitors |
| CN104523654A (en) * | 2014-12-15 | 2015-04-22 | 北京红太阳药业有限公司 | Dexlansoprazole sustained-release capsule and preparation method thereof |
| CN104606146A (en) * | 2015-02-11 | 2015-05-13 | 苏州大学 | Esomeprazole enteric coated pellet preparation and preparation method thereof |
| WO2017017615A1 (en) * | 2015-07-28 | 2017-02-02 | Zim Laboratories Ltd. | Novel dual delayed release oral composition of dexlansoprazole |
| US20190046459A1 (en) * | 2016-02-29 | 2019-02-14 | Yoo Young Pharm. Co., Ltd. | Preparation Containing Esomeprazole |
| CN111214457A (en) * | 2020-03-31 | 2020-06-02 | 吴尔朗 | Esomeprazole magnesium enteric-coated pellet preparation and preparation method thereof |
-
2020
- 2020-09-21 CN CN202010991585.3A patent/CN111991367A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080095853A1 (en) * | 2004-11-04 | 2008-04-24 | Niclas Clemmensen | Modified Release For Proton Pump Inhibitors |
| CN104523654A (en) * | 2014-12-15 | 2015-04-22 | 北京红太阳药业有限公司 | Dexlansoprazole sustained-release capsule and preparation method thereof |
| CN104606146A (en) * | 2015-02-11 | 2015-05-13 | 苏州大学 | Esomeprazole enteric coated pellet preparation and preparation method thereof |
| WO2017017615A1 (en) * | 2015-07-28 | 2017-02-02 | Zim Laboratories Ltd. | Novel dual delayed release oral composition of dexlansoprazole |
| US20190046459A1 (en) * | 2016-02-29 | 2019-02-14 | Yoo Young Pharm. Co., Ltd. | Preparation Containing Esomeprazole |
| CN111214457A (en) * | 2020-03-31 | 2020-06-02 | 吴尔朗 | Esomeprazole magnesium enteric-coated pellet preparation and preparation method thereof |
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Application publication date: 20201127 |