CN113521067B - Famotidine zinc gluconate preparation composition and preparation method thereof - Google Patents
Famotidine zinc gluconate preparation composition and preparation method thereof Download PDFInfo
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- CN113521067B CN113521067B CN202110765796.XA CN202110765796A CN113521067B CN 113521067 B CN113521067 B CN 113521067B CN 202110765796 A CN202110765796 A CN 202110765796A CN 113521067 B CN113521067 B CN 113521067B
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- famotidine
- calcium
- zinc gluconate
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- cellulose
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- 238000002360 preparation method Methods 0.000 title claims abstract description 87
- 229960001596 famotidine Drugs 0.000 title claims abstract description 75
- 235000011478 zinc gluconate Nutrition 0.000 title claims abstract description 74
- 229960000306 zinc gluconate Drugs 0.000 title claims abstract description 74
- 239000011670 zinc gluconate Substances 0.000 title claims abstract description 74
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 title claims abstract description 66
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 title claims abstract description 65
- 239000000203 mixture Substances 0.000 title claims abstract description 47
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 39
- 239000011575 calcium Substances 0.000 claims abstract description 39
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 39
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 35
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 35
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 35
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 35
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 claims abstract description 20
- 239000000853 adhesive Substances 0.000 claims abstract description 18
- 230000001070 adhesive effect Effects 0.000 claims abstract description 18
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 17
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 17
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 17
- 239000000314 lubricant Substances 0.000 claims abstract description 10
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- 235000001465 calcium Nutrition 0.000 claims abstract description 4
- 229960005069 calcium Drugs 0.000 claims abstract description 3
- 239000008187 granular material Substances 0.000 claims description 50
- 238000002156 mixing Methods 0.000 claims description 27
- 239000011230 binding agent Substances 0.000 claims description 21
- 238000005303 weighing Methods 0.000 claims description 19
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 16
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 15
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 15
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 15
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 15
- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 15
- 239000002775 capsule Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 10
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 10
- 239000002245 particle Substances 0.000 claims description 9
- 239000013022 formulation composition Substances 0.000 claims description 8
- 235000019359 magnesium stearate Nutrition 0.000 claims description 8
- 238000000576 coating method Methods 0.000 claims description 6
- 239000007888 film coating Substances 0.000 claims description 5
- 238000009501 film coating Methods 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 238000007906 compression Methods 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims 1
- 238000004090 dissolution Methods 0.000 abstract description 20
- 239000003814 drug Substances 0.000 abstract description 16
- 230000000694 effects Effects 0.000 abstract description 11
- 208000008469 Peptic Ulcer Diseases 0.000 abstract description 10
- 208000011906 peptic ulcer disease Diseases 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 7
- 230000002195 synergetic effect Effects 0.000 abstract description 4
- 239000000945 filler Substances 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 3
- 230000000052 comparative effect Effects 0.000 description 9
- -1 famotidine zinc gluconate compound Chemical class 0.000 description 9
- 238000001035 drying Methods 0.000 description 8
- 239000007779 soft material Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 208000000718 duodenal ulcer Diseases 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 208000007107 Stomach Ulcer Diseases 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 230000027119 gastric acid secretion Effects 0.000 description 3
- 201000005917 gastric ulcer Diseases 0.000 description 3
- 238000003825 pressing Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 206010042220 Stress ulcer Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 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 description 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 201000000052 gastrinoma Diseases 0.000 description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 208000000689 peptic esophagitis Diseases 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 229940091251 zinc supplement Drugs 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010061459 Gastrointestinal ulcer Diseases 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 229940122957 Histamine H2 receptor antagonist Drugs 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 206010046274 Upper gastrointestinal haemorrhage Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 201000008629 Zollinger-Ellison syndrome Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000002857 effect on ulcer Effects 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 229960000620 ranitidine Drugs 0.000 description 1
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
-
- 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
- A61K31/28—Compounds containing heavy metals
- A61K31/315—Zinc compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
-
- 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
- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
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- 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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- Chemical & Material Sciences (AREA)
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- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of medicines, and particularly relates to a famotidine zinc gluconate preparation composition and a preparation method thereof. The famotidine zinc gluconate preparation composition comprises famotidine, zinc gluconate, microcrystalline cellulose, calcium hydrophosphate, hydroxypropyl cellulose, carboxymethyl cellulose calcium and a lubricant. The famotidine zinc gluconate preparation composition provided by the invention can not only exert the synergistic effect of famotidine and zinc gluconate, improve the curative effect of the medicine and obtain better effect of treating peptic ulcer; and the medicine taking frequency of patients can be reduced, and the compliance of the patients taking the medicines is improved. Meanwhile, the preparation composition adopts microcrystalline cellulose and calcium hydrophosphate as fillers, carboxymethyl cellulose calcium as a disintegrating agent and hydroxypropyl cellulose as an adhesive, and the content of the auxiliary materials is adjusted, so that good dissolution performance and stability are obtained, and the problems of slow dissolution and poor stability of the existing single-component preparation are effectively solved.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a famotidine zinc gluconate preparation composition and a preparation method thereof.
Background
Digestive tract diseases are common diseases and frequently-occurring diseases, wherein the incidence of diseases of the stomach and the duodenum is the highest, and the number of the diseased people accounts for more than 10 percent of the world population. Gastrointestinal ulcer is one of the main diseases affecting human health at present, so that finding anti-ulcer medicines with good curative effect and low price is always a hot point in the field of medicine research and development.
The chemical formula of zinc gluconate is C 12 H 22 O 14 Zn is a common organic zinc supplement, has small irritation to gastric mucosa, is easy to be absorbed by human body in vivo, and has high absorption rate and good solubility.
Famotidine is a histamine H2 receptor antagonist, can inhibit gastric acid secretion, and is suitable for gastric and duodenal ulcer, reflux esophagitis, upper gastrointestinal hemorrhage, zollinger-Ellison syndrome and other symptoms. Famotidine has obvious gastric acid secretion inhibiting effect, 30 times stronger than cimetidine and 6-10 times stronger than ranitidine, and may be used clinically in treating gastric and duodenal ulcer, stress ulcer, acute gastromucosae hemorrhage, gastrinoma, reflux esophagitis, etc. and through blood circulation to take effect.
The zinc gluconate is used as zinc supplement, is an indispensable substance for repairing tissues and repairing wounds and has a repairing effect on ulcer surfaces of body tissues. Famotidine enters blood to inhibit gastric acid secretion and better improve symptoms such as gastric ulcer, duodenal ulcer and stress ulcer. The two medicines have good synergistic effect, and can enhance healing effect of treating peptic ulcer, inhibit helicobacter pylori, and increase eradication rate. The existing single-component oral solid preparation of famotidine and zinc gluconate sold in the market usually adopts auxiliary materials such as corn starch, dextrin, sodium carboxymethyl starch and the like, is slow in disintegration and dissolution, influences absorption in vivo, is poor in long-term stability, and can cause the problem of degradation of effective components after being placed for a period of time. And the single-prescription preparation is not favorable for the compliance of patients taking the medicine. Therefore, the development of a famotidine zinc gluconate compound preparation with high dissolution speed and good stability is urgently needed.
Disclosure of Invention
In order to obtain the famotidine zinc gluconate compound preparation with high dissolution speed and good stability, the famotidine zinc gluconate preparation composition is designed and prepared through extensive and intensive research, and the dissolution effect and the stability of the preparation composition are researched.
The invention aims to provide a famotidine zinc gluconate preparation composition.
The invention also aims to provide a preparation method of the famotidine zinc gluconate preparation composition.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the invention provides a famotidine zinc gluconate preparation composition which comprises the following components in percentage by mass:
the famotidine zinc gluconate preparation composition combines the treatment effects of famotidine and zinc gluconate, exerts the synergistic effect of the famotidine and the zinc gluconate and can obtain a better effect of treating peptic ulcer. Meanwhile, compared with two single preparations, the compound preparation can reduce the administration frequency of patients and effectively provide the patient medication compliance.
The preparation composition provided by the invention adopts 25-35% of microcrystalline cellulose and 20-35% of calcium hydrogen phosphate as filler, 5-10% of carboxymethyl cellulose calcium as disintegrant and 1-10% of hydroxypropyl cellulose as adhesive by mass percentage, thereby obtaining good dissolution performance and stability, and effectively solving the problems of slow dissolution and poor stability of the existing single preparation.
The preparation composition provided by the invention can be prepared into various common dosage forms such as tablets, pills, capsules, granules and the like according to conventional preparation methods in the pharmaceutical field such as mixing, dissolving, freeze-drying and the like, and is convenient for clinical use of patients.
In the application process of treating peptic ulcer, the preparation composition provided by the invention is used for realizing the treatment effect by means of administering a therapeutically effective amount of the preparation composition provided by the invention to a patient needing to treat peptic ulcer. The preparation composition provided by the invention can be used as a treatment medicament for treating peptic ulcer independently, and can also be used in combination with other conventional treatment medicaments for treating peptic ulcer.
The therapeutically effective amount of the formulation composition provided by the present invention for the treatment of peptic ulcer depends on many factors. May vary depending on the specific disease site of the peptic ulcer that needs to be treated, which can be determined by those skilled in the art without undue experimentation. The actual treatment will also take into account factors such as the age and weight of the patient, the severity of the condition, the particular mode of administration, etc., and will ultimately be at the discretion of the attendant physician or clinician.
As a preferable scheme of the preparation composition of the present invention, the preparation composition comprises the following components by mass:
further, the lubricant is at least one of talcum powder, magnesium stearate, calcium stearate and superfine silica gel powder.
Further, the preparation composition is a solid oral preparation.
The preparation composition provided by the invention can be prepared into various common solid oral dosage forms, such as tablets, granules, pills, capsules and the like, according to a conventional preparation method in the pharmaceutical field, and is convenient for patients to carry and take.
Further, the preparation composition further comprises a film coating agent.
The film coating agent used in the invention can be selected from the variety commonly used in pharmacy, such as Opadry series film coating powder of Calekang company. The amount of film coating agent is readily available to those skilled in the art in view of the prior art.
In a second aspect, the invention provides a preparation method of a famotidine zinc gluconate preparation composition, which comprises the following steps:
weighing famotidine, zinc gluconate, microcrystalline cellulose, calcium hydrophosphate, hydroxypropyl cellulose, carboxymethylcellulose calcium and a lubricant according to the prescription amount;
adding water into hydroxypropyl cellulose to prepare a binder solution, and weighing the binder solution into a first part of binder solution and a second part of binder solution;
dividing microcrystalline cellulose into a first part of microcrystalline cellulose and a second part of microcrystalline cellulose by weighing; calcium hydrophosphate is divided into a first part of calcium hydrophosphate and a second part of calcium hydrophosphate by weighing; the calcium carboxymethyl cellulose is divided into a first part of calcium carboxymethyl cellulose and a second part of calcium carboxymethyl cellulose by weighing;
uniformly mixing famotidine, a first part of microcrystalline cellulose, a first part of calcium hydrophosphate and a first part of carboxymethyl cellulose calcium, and adding a first part of adhesive solution to prepare famotidine particles;
uniformly mixing zinc gluconate, a second part of microcrystalline cellulose, a second part of calcium hydrophosphate and a second part of calcium carboxymethyl cellulose, and adding a second part of adhesive solution to prepare zinc gluconate granules;
and uniformly mixing the famotidine granules, the zinc gluconate granules and the lubricant to obtain the granules.
Further, the granules are prepared into tablets through a compression process.
Further, the tablet is made into a coated tablet by a coating process.
Further, the granules are filled into a shell of a medicinal capsule to prepare the capsule.
The medicinal capsule shell adopted by the invention can be prepared by adopting raw materials and preparation processes which are commonly used in pharmacy. The size can be determined according to the content of the pharmaceutically active ingredient in the granules and the effective dose of the pharmaceutically active ingredient required to be contained in a single capsule.
The preparation method of the preparation composition provided by the invention has the advantages of simple operation of the whole preparation process, easy control, low requirements on production equipment and suitability for industrial large-scale production.
The production equipment, operating conditions and the like used in the preparation process can be routinely selected by those skilled in the art. The formulation compositions provided by the present invention may also be conveniently prepared by optionally combining various synthetic methods described in the present specification or known in the art, and such combinations may be readily carried out by those skilled in the art to which the present invention pertains.
The beneficial effects of the invention include:
the invention provides a famotidine zinc gluconate preparation composition, which can not only exert the synergistic effect of famotidine and zinc gluconate, improve the curative effect of the medicine and obtain better effect of treating peptic ulcer; and the medicine frequency of patients can be reduced, and the compliance of the patients taking the medicines is improved. Meanwhile, the preparation composition adopts microcrystalline cellulose and calcium hydrophosphate as fillers, carboxymethyl cellulose calcium as a disintegrating agent and hydroxypropyl cellulose as an adhesive, and obtains good dissolution performance and stability by adjusting the content of the various auxiliary materials, thereby effectively solving the problems of slow dissolution and poor stability of the existing single-prescription preparation. The preparation composition provided by the invention can be prepared into solid oral preparations such as tablets, coated tablets, capsules, granules and the like by a proper preparation process, and is convenient for patients to take.
Detailed Description
In order to make the technical problems, technical solutions and advantageous effects to be solved by the present invention more apparent, the present invention is further described in detail below with reference to specific embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present patent and do not limit the scope of the invention in any way.
The famotidine zinc gluconate preparation composition provided by the invention can be prepared from the following components in percentage by mass:
for example, 5kg of hydroxypropyl cellulose is added with water to make an 8% binder solution; uniformly mixing 8kg of famotidine, 15kg of microcrystalline cellulose, 12kg of calcium hydrophosphate and 4kg of carboxymethylcellulose calcium, and adding half of adhesive solution to prepare famotidine granules; mixing zinc gluconate 10kg, microcrystalline cellulose 15kg, calcium hydrogen phosphate 12kg and carboxymethylcellulose calcium 4kg, adding the other half of the binder solution, and making into zinc gluconate granule; the famotidine granules, the zinc gluconate granules and 2kg of magnesium stearate are evenly mixed to obtain granules.
For another example, the granules prepared by the above process can be made into tablets by a compression process.
For another example, a capsule can be obtained by encapsulating the granules prepared by the above process into a pharmaceutical capsule shell.
The famotidine zinc gluconate preparation composition provided by the invention can also comprise the following components in percentage by mass:
for example, 5kg of hydroxypropyl cellulose is added with water to make an 8% binder solution; mixing 8kg of famotidine, 15kg of microcrystalline cellulose, 12kg of calcium hydrophosphate and 4kg of carboxymethylcellulose calcium uniformly, and adding half of adhesive solution to prepare famotidine granules; mixing zinc gluconate 10kg, microcrystalline cellulose 15kg, calcium hydrogen phosphate 12kg and carboxymethylcellulose calcium 4kg, adding the other half of the binder solution, and making into zinc gluconate granule; uniformly mixing famotidine granules, zinc gluconate granules and 2kg of talcum powder to obtain granules; making the granules into tablets by a pressing process; coating the tablet to obtain coated tablet.
The invention is described in more detail by referring to a part of the tests, which are carried out in sequence, and the following detailed description is given by combining specific examples:
unless defined otherwise, technical terms used in the following examples have the same meanings as commonly understood by one of ordinary skill in the art to which the present invention belongs. The reagents used in the following examples, unless otherwise specified, are all conventional biochemical reagents; the raw materials, instruments, equipment and the like used in the following examples are either commercially available or available by existing methods; the dosage of the reagent is the dosage of the reagent in the conventional experiment operation if no special instruction is provided; the experimental methods are conventional methods unless otherwise specified.
Example 1
A famotidine zinc gluconate preparation composition is prepared from the following components in parts by mass:
the preparation method of the preparation composition comprises the following steps:
s1, weighing 3.5kg of hydroxypropyl cellulose, and adding water to prepare a 6% adhesive solution;
s2, mixing 5kg of famotidine, 16.5kg of microcrystalline cellulose, 15kg of calcium hydrogen phosphate and 5kg of carboxymethylcellulose calcium in a wet granulator for 10min, adding half of a binder solution, preparing a soft material, granulating by a 20-mesh sieve, drying by a fluidized bed until the moisture content is 2-3%, and granulating by the 20-mesh sieve to prepare famotidine granules;
s3, mixing 17.5kg of zinc gluconate, 16.5kg of microcrystalline cellulose, 15kg of calcium hydrophosphate and 5kg of carboxymethylcellulose calcium in a wet granulator for 10min, adding the other half of the adhesive solution to prepare a soft material, granulating by 20 meshes, drying by adopting a fluidized bed until the moisture content is 2-3%, and granulating by 18 meshes to prepare zinc gluconate granules;
s4, adding the famotidine granules and the zinc gluconate granules into a three-dimensional mixer, adding 1kg of magnesium stearate, and uniformly mixing to obtain the granules.
Example 2
A famotidine zinc gluconate preparation composition is prepared from the following components in parts by mass:
the preparation method of the preparation composition comprises the following steps:
s1, weighing 1kg of hydroxypropyl cellulose, and adding water to prepare a 6% adhesive solution;
s2, mixing 5kg of famotidine, 11kg of microcrystalline cellulose, 10kg of calcium hydrogen phosphate and 2.5kg of carboxymethylcellulose calcium in a wet granulator for 10min, adding half of the binder solution, preparing a soft material, granulating by a 20-mesh sieve, drying by a fluidized bed until the moisture content is 2-3%, and granulating by the 20-mesh sieve to obtain famotidine granules;
s3, mixing 10kg of zinc gluconate, 11kg of microcrystalline cellulose, 10kg of calcium hydrogen phosphate and 2.5kg of carboxymethylcellulose calcium in a wet granulator for 10min, adding the other half of the adhesive solution, preparing a soft material, granulating by a 20-mesh sieve, drying by a fluidized bed until the water content is 2-3%, and granulating by a 18-mesh sieve to prepare zinc gluconate granules;
s4, adding the famotidine particles and the zinc gluconate particles into a three-dimensional mixer, adding 0.1kg of magnesium stearate, and uniformly mixing to obtain granules;
s5, filling the granules by adopting a capsule filling machine to obtain capsules, and controlling the filling quantity difference within 5%.
Example 3
A famotidine zinc gluconate preparation composition is prepared from the following components in parts by mass:
the preparation method of the preparation composition comprises the following steps:
s1, weighing 10kg of hydroxypropyl cellulose, and adding water to prepare a 6% adhesive solution;
s2, mixing 10kg of famotidine, 16.5kg of microcrystalline cellulose, 17.5kg of calcium hydrogen phosphate and 3.5kg of carboxymethylcellulose calcium in a wet granulator for 10min, adding half of a binder solution, preparing a soft material, granulating by a 20-mesh sieve, drying by a fluidized bed until the moisture content is 2-3%, and granulating by the 20-mesh sieve to prepare famotidine granules;
s3, mixing 30kg of zinc gluconate, 16.5kg of microcrystalline cellulose, 17.5kg of calcium hydrophosphate and 3.5kg of carboxymethylcellulose calcium in a wet granulator for 10min, adding the other half of the binder solution, preparing a soft material, granulating by 20 meshes, drying by adopting a fluidized bed until the water content is 2-3%, and granulating by 18 meshes to prepare zinc gluconate granules;
s4, adding the famotidine particles and the zinc gluconate particles into a three-dimensional mixer, adding 5kg of magnesium stearate, and uniformly mixing to obtain granules;
s5, pressing the granules into tablets by adopting a rotary tablet press, and controlling the hardness of the tablets to be 6-10kg.
Example 4
A famotidine zinc gluconate preparation composition is prepared from the following components in parts by mass:
the preparation method of the preparation composition comprises the following steps:
s1, weighing 3.5kg of hydroxypropyl cellulose, and adding water to prepare a 6% adhesive solution;
s2, mixing 5kg of famotidine, 16.5kg of microcrystalline cellulose, 15kg of calcium hydrogen phosphate and 5kg of carboxymethylcellulose calcium in a wet granulator for 10min, adding half of a binder solution, preparing a soft material, granulating by a 20-mesh sieve, drying by a fluidized bed until the moisture content is 2-3%, and granulating by the 20-mesh sieve to prepare famotidine granules;
s3, mixing 17.5kg of zinc gluconate, 16.5kg of microcrystalline cellulose, 15kg of calcium hydrophosphate and 5kg of carboxymethylcellulose calcium in a wet granulator for 10min, adding the other half of the adhesive solution to prepare a soft material, granulating by 20 meshes, drying by adopting a fluidized bed until the moisture content is 2-3%, and granulating by 18 meshes to prepare zinc gluconate granules;
s4, adding the famotidine granules and the zinc gluconate granules into a three-dimensional mixer, adding 1kg of magnesium stearate, and uniformly mixing to obtain granules;
s5, pressing the granules into tablets by adopting a rotary tablet press, controlling the hardness of the tablets to be 6-10kg, putting the pressed plain tablets into a high-efficiency coating machine, and then coating, wherein the weight of the coating is controlled to be increased by 2-3%.
Comparative example 1
Different from the embodiment 4, the famotidine zinc gluconate compound preparation is prepared from the following components in parts by mass:
comparative example 2
Different from the embodiment 4, the famotidine zinc gluconate compound preparation is prepared from the following components in parts by mass:
comparative example 3
Different from the embodiment 4, the famotidine zinc gluconate compound preparation is prepared from the following components in parts by mass:
comparative example 4
Different from the embodiment 4, the famotidine zinc gluconate compound preparation is prepared from the following components in parts by mass:
comparative example 5
Different from the embodiment 4, the famotidine zinc gluconate compound preparation is prepared from the following components in parts by mass:
comparative example 6
Different from the embodiment 4, the famotidine zinc gluconate compound preparation is prepared from the following components in parts by mass:
comparative example 7
Different from the embodiment 4, the famotidine zinc gluconate compound preparation is prepared from the following components in parts by mass:
evaluation of Performance
1. Evaluation of dissolution Properties
The preparation compositions of examples 1 to 4 were compared with the compound preparations and two single preparations of comparative examples 1 to 7, and the in vitro dissolution of famotidine and zinc gluconate was measured, and the test results are shown in tables 1 and 2, respectively.
Wherein: the single-component preparation famotidine tablet is famotidine tablet (specification is 20 mg) produced by Astelasp Pharma Inc. and the single-component preparation zinc gluconate tablet is zinc gluconate tablet (specification is 70 mg) produced by Beida medicine corporation.
Dissolution was determined by reference to the dissolution and release assay (first method of general rule 0931).
The instrument comprises the following steps: ultraviolet spectrophotometer and dissolution rate tester
Dissolution medium: hydrochloric acid solution of pH1.0
Volume of dissolution medium: 900mL basket method
Rotating speed: 75 revolutions per minute
Sampling time: 5min, 10min, 15min, 30min, 45min
TABLE 1 detection results of famotidine dissolution in hydrochloric acid solution with pH1.0
TABLE 2 test results of zinc gluconate dissolution in hydrochloric acid solution of pH1.0
As can be seen from tables 1 and 2, compared with the compound preparation, famotidine tablet and zinc gluconate tablet of comparative examples 1-7, the famotidine and zinc gluconate tablets in the preparation compositions of examples 1-4 are dissolved out more quickly, the dissolution amount in 15 minutes can reach more than 85%, and the preparation compositions have better dissolution performance obviously.
Therefore, the famotidine zinc gluconate preparation composition provided by the invention adopts the combination of 25-35% of microcrystalline cellulose, 20-35% of calcium hydrogen phosphate, 5-10% of carboxymethyl cellulose and 1-10% of hydroxypropyl cellulose in percentage by mass, so that the preparation composition has excellent dissolution performance.
2. Evaluation of stability
Taking the preparation compositions of the examples 1-4, carrying out accelerated test investigation on samples according to the requirements of the four stability guidelines in the 2020 version of Chinese pharmacopoeia, carrying out accelerated test investigation on samples under the conditions of test temperature of (40 +/-2) DEG C and relative humidity of (75 +/-5)% and having test results shown in Table 3.
Table 3 stability test results of formulation compositions
As can be seen from Table 3, the formulation compositions of examples 1 to 4 all had good stability.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (7)
1. The famotidine zinc gluconate preparation composition is characterized by comprising the following components in percentage by mass:
the lubricant is magnesium stearate;
the preparation composition is prepared by the following preparation method:
weighing famotidine, zinc gluconate, microcrystalline cellulose, calcium hydrophosphate, hydroxypropyl cellulose, calcium carboxymethylcellulose and a lubricant according to the prescription amount;
adding water into hydroxypropyl cellulose to prepare a binder solution, and weighing the binder solution into a first part of binder solution and a second part of binder solution;
dividing microcrystalline cellulose into a first part of microcrystalline cellulose and a second part of microcrystalline cellulose by weighing; calcium hydrophosphate is divided into a first part of calcium hydrophosphate and a second part of calcium hydrophosphate by weighing; the calcium carboxymethyl cellulose is divided into a first part of calcium carboxymethyl cellulose and a second part of calcium carboxymethyl cellulose by weighing;
uniformly mixing famotidine, a first part of microcrystalline cellulose, a first part of calcium hydrophosphate and a first part of carboxymethyl cellulose calcium, and adding a first part of adhesive solution to prepare famotidine particles;
uniformly mixing zinc gluconate, a second part of microcrystalline cellulose, a second part of calcium hydrophosphate and a second part of calcium carboxymethyl cellulose, and adding a second part of adhesive solution to prepare zinc gluconate granules;
uniformly mixing the famotidine particles, the zinc gluconate particles and the lubricant to obtain granules.
2. The formulation composition as claimed in claim 1, wherein the formulation composition is a solid oral formulation.
3. The formulation composition of claim 2, further comprising a film coating agent.
4. A method of preparing the formulation composition of claim 2, comprising:
weighing famotidine, zinc gluconate, microcrystalline cellulose, calcium hydrogen phosphate, hydroxypropyl cellulose, calcium carboxymethyl cellulose and a lubricant according to the prescription amount, wherein the lubricant is magnesium stearate;
adding water into hydroxypropyl cellulose to prepare a binder solution, and weighing the binder solution into a first part of binder solution and a second part of binder solution;
dividing microcrystalline cellulose into a first part of microcrystalline cellulose and a second part of microcrystalline cellulose by weighing; calcium hydrophosphate is divided into a first part of calcium hydrophosphate and a second part of calcium hydrophosphate by weighing; the calcium carboxymethyl cellulose is divided into a first part of calcium carboxymethyl cellulose and a second part of calcium carboxymethyl cellulose by weighing;
uniformly mixing famotidine, a first part of microcrystalline cellulose, a first part of calcium hydrophosphate and a first part of carboxymethyl cellulose calcium, and adding a first part of adhesive solution to prepare famotidine particles;
uniformly mixing zinc gluconate, a second part of microcrystalline cellulose, a second part of calcium hydrophosphate and a second part of calcium carboxymethylcellulose, and adding a second part of adhesive solution to prepare zinc gluconate granules;
and uniformly mixing the famotidine granules, the zinc gluconate granules and the lubricant to obtain the granules.
5. The method of claim 4, wherein the granules are formed into tablets by a compression process.
6. The method of claim 5, wherein the tablet is subjected to a coating process to form a coated tablet.
7. The method of claim 4, wherein the granules are encapsulated in a pharmaceutical capsule shell.
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