WO2024221579A1 - Aluminum magnesium carbonate double-layer tablet and preparation method therefor - Google Patents
Aluminum magnesium carbonate double-layer tablet and preparation method therefor Download PDFInfo
- Publication number
- WO2024221579A1 WO2024221579A1 PCT/CN2023/102203 CN2023102203W WO2024221579A1 WO 2024221579 A1 WO2024221579 A1 WO 2024221579A1 CN 2023102203 W CN2023102203 W CN 2023102203W WO 2024221579 A1 WO2024221579 A1 WO 2024221579A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- layer
- parts
- hydrotalcite
- sustained
- aluminum carbonate
- Prior art date
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- UJOHNXQDVUADCG-UHFFFAOYSA-L aluminum;magnesium;carbonate Chemical compound [Mg+2].[Al+3].[O-]C([O-])=O UJOHNXQDVUADCG-UHFFFAOYSA-L 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title description 4
- 238000013268 sustained release Methods 0.000 claims abstract description 67
- 239000012730 sustained-release form Substances 0.000 claims abstract description 67
- 239000003814 drug Substances 0.000 claims abstract description 20
- 229940079593 drug Drugs 0.000 claims abstract description 19
- 230000002496 gastric effect Effects 0.000 claims abstract description 17
- 239000007884 disintegrant Substances 0.000 claims abstract description 15
- 239000004088 foaming agent Substances 0.000 claims abstract description 15
- 239000000945 filler Substances 0.000 claims abstract description 14
- 239000000463 material Substances 0.000 claims abstract description 10
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 8
- 238000003825 pressing Methods 0.000 claims abstract description 3
- PPQREHKVAOVYBT-UHFFFAOYSA-H dialuminum;tricarbonate Chemical compound [Al+3].[Al+3].[O-]C([O-])=O.[O-]C([O-])=O.[O-]C([O-])=O PPQREHKVAOVYBT-UHFFFAOYSA-H 0.000 claims description 138
- 229940118662 aluminum carbonate Drugs 0.000 claims description 69
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 claims description 64
- 229960001545 hydrotalcite Drugs 0.000 claims description 64
- 229910001701 hydrotalcite Inorganic materials 0.000 claims description 64
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 40
- 239000002994 raw material Substances 0.000 claims description 26
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 24
- 239000008101 lactose Substances 0.000 claims description 23
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 22
- 229930195725 Mannitol Natural products 0.000 claims description 22
- 239000000594 mannitol Substances 0.000 claims description 22
- 235000010355 mannitol Nutrition 0.000 claims description 22
- 108010010803 Gelatin Proteins 0.000 claims description 20
- 239000008273 gelatin Substances 0.000 claims description 20
- 229920000159 gelatin Polymers 0.000 claims description 20
- 235000019322 gelatine Nutrition 0.000 claims description 20
- 235000011852 gelatine desserts Nutrition 0.000 claims description 20
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 20
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 20
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 20
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 20
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 20
- 239000011812 mixed powder Substances 0.000 claims description 18
- 235000021355 Stearic acid Nutrition 0.000 claims description 17
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 17
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 17
- 239000008117 stearic acid Substances 0.000 claims description 17
- 239000000499 gel Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 14
- 239000000654 additive Substances 0.000 claims description 13
- 230000000996 additive effect Effects 0.000 claims description 11
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 10
- 239000008187 granular material Substances 0.000 claims description 10
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 10
- 238000012545 processing Methods 0.000 claims description 6
- 230000008961 swelling Effects 0.000 claims description 6
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- 238000012377 drug delivery Methods 0.000 claims description 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 3
- 229920000084 Gum arabic Polymers 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- 239000000205 acacia gum Substances 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 235000013871 bee wax Nutrition 0.000 claims description 2
- 239000012166 beeswax Substances 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- -1 expanders Substances 0.000 claims description 2
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 2
- 229920003063 hydroxymethyl cellulose Polymers 0.000 claims description 2
- 229940031574 hydroxymethyl cellulose Drugs 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 2
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 241000978776 Senegalia senegal Species 0.000 claims 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims 1
- 238000001647 drug administration Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 12
- 210000002784 stomach Anatomy 0.000 abstract description 7
- 239000002253 acid Substances 0.000 abstract description 6
- 208000007107 Stomach Ulcer Diseases 0.000 abstract description 5
- 208000000718 duodenal ulcer Diseases 0.000 abstract description 5
- 239000003826 tablet Substances 0.000 description 50
- 235000017550 sodium carbonate Nutrition 0.000 description 17
- 238000012360 testing method Methods 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 238000004090 dissolution Methods 0.000 description 13
- 210000004051 gastric juice Anatomy 0.000 description 12
- 230000007774 longterm Effects 0.000 description 11
- 230000000052 comparative effect Effects 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- 210000004211 gastric acid Anatomy 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- 125000002887 hydroxy group Chemical class [H]O* 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000013112 stability test Methods 0.000 description 4
- 239000000872 buffer Substances 0.000 description 3
- 239000001569 carbon dioxide Substances 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 238000007922 dissolution test Methods 0.000 description 3
- 208000007882 Gastritis Diseases 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000001458 anti-acid effect Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 201000005917 gastric ulcer Diseases 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000001550 time effect Effects 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 206010015137 Eructation Diseases 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 208000027687 belching Diseases 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 208000023652 chronic gastritis Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 208000024798 heartburn Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
Classifications
-
- 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/10—Carbonates; Bicarbonates
-
- 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
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
-
- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/2063—Proteins, e.g. gelatin
-
- 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
-
- 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
Definitions
- the invention relates to the technical field of pharmaceuticals, and in particular to a hydrotalcite double-layer tablet and a preparation method thereof.
- Aluminum carbonate granules are a drug used for acute and chronic gastritis, gastric ulcer, duodenal ulcer, reflux esophagitis, stomach discomfort symptoms related to gastric acid, such as stomach pain, heartburn, acidic belching, fullness, prevention of gastric mucosal damage caused by non-steroidal drugs, etc.
- aluminum carbonate granules, aluminum carbonate suspension, aluminum carbonate chewable tablets, and aluminum carbonate co-dry gel on the market.
- aluminum carbonate granules, tablets, and aluminum carbonate co-dry gel are common products with basically the same principle. The disadvantage is that the retention time in the stomach is not long.
- the present invention aims to provide a hydrotalcite double-layer tablet.
- Another object of the present invention is to provide a method for preparing a hydrotalcite double-layer tablet, which solves the problems of poor uniformity in the double-layer tablet structure and disordered release of hydrotalcite between the ordinary layer and the sustained-release layer, so that the hydrotalcite double-layer tablet can achieve the effect of timely treatment and long-term maintenance of the therapeutic effect.
- a double-layer aluminum carbonate tablet characterized in that the double-layer tablet is obtained by pressing a common aluminum carbonate layer and a sustained-release aluminum carbonate layer, wherein the common aluminum carbonate layer contains aluminum carbonate as the main drug, and the auxiliary materials are fillers and disintegrants, and the sustained-release aluminum carbonate layer contains aluminum carbonate as the main drug, and the auxiliary materials are administration rate regulators, gastric floating additives, expanders, foaming agents and hydrophilic gels.
- the filler includes one or more of lactose, mannitol, and microcrystalline cellulose.
- the disintegrant is one or more of low-substituted hydroxymethyl cellulose and sodium carboxymethyl starch.
- the administration rate regulator is one or more of lactose and mannitol.
- the gastric floating additive includes one or more of glyceryl monostearate, stearyl alcohol, stearic acid and beeswax.
- the swelling agent is one or more of gelatin and gum arabic.
- the foaming agent is any one of sodium carbonate and sodium bicarbonate.
- the hydrophilic gel includes one or more of hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (CMC-Na), polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA).
- HPMC hydroxypropylmethylcellulose
- CMC-Na sodium carboxymethylcellulose
- PVP polyvinyl pyrrolidone
- PVA polyvinyl alcohol
- hydrotalcite is present in an amount of 150 to 200 parts
- filler is present in an amount of 60 to 77 parts
- disintegrant is present in an amount of 30 to 60 parts.
- aluminum carbonate sustained-release layer aluminum carbonate is 50 to 80 parts, the administration rate regulator is 20 to 30 parts, the gastric floating additive is 130 to 170 parts, the foaming agent is 80 to 150 parts, the expander is 85 to 105 parts, and the hydrophilic gel is 30 to 60 parts.
- the filler in the auxiliary materials is lactose, and the disintegrant is low-substituted hydroxypropyl cellulose.
- aluminum carbonate is the main drug
- the administration rate regulator in the auxiliary materials is mannitol
- the gastric floating additive is stearic acid
- the swelling agent is gelatin
- the foaming agent is sodium carbonate
- the hydrophilic gel is HPMC.
- hydrotalcite in the ordinary hydrotalcite layer, hydrotalcite is present in an amount of 170 to 200 parts, lactose is present in an amount of 60 to 77 parts, and low-substituted hydroxypropyl cellulose is present in an amount of 30 to 60 parts.
- hydrotalcite sustained-release layer hydrotalcite is 50-80 parts, mannitol is 20-30 parts, stearic acid is 130-170 parts, sodium carbonate is 80-150 parts, gelatin is 85-105 parts, and HPMC is 30-60 parts.
- the basic principle of the aluminum carbonate double-layer tablet for treating gastric ulcer and duodenal ulcer is that when the ordinary layer of aluminum carbonate encounters gastric juice, it quickly disintegrates under the action of the disintegrant low-substituted hydroxypropyl cellulose and is peeled off from the sustained-release layer of aluminum carbonate. At the same time, the gelatin in the sustained-release layer of aluminum carbonate rapidly expands in volume under the action of the hydrophilic gel hydroxypropyl methylcellulose after encountering gastric juice.
- the sustained-release layer quickly falls off from the surface of the ordinary layer of aluminum carbonate, and the ordinary layer sinks and adheres to the stomach surface under the gravity of aluminum carbonate, quickly takes effect to protect the gastric mucosa from being eroded by gastric acid, and aluminum carbonate and gastric acid
- the reaction generates gas to form a boosting force, which pushes the aluminum carbonate sustained-release layer in the stomach in an undirected manner, so that the sustained-release layer can release drugs at different positions in the stomach.
- the mannitol/lactose in the sustained-release layer in the wandering state dissolves evenly after meeting water, forming certain evenly distributed pores on the surface of the sustained-release layer, so that gastric acid and the foaming agent sodium carbonate are fully in contact, and the reaction generates carbon dioxide.
- the carbon dioxide gas and stearic acid cooperate to allow the sustained-release layer to float in the stomach for a long time, forming a gastric floating tablet, so that the carbon dioxide generated by the reaction shuttles evenly in the sustained-release layer, further penetrates the pores generated by the dissolution of mannitol to form holes, and forms a sustained-release channel, which regulates the release rate of aluminum carbonate in the sustained-release layer, achieves a continuous and slow release of the aluminum carbonate component, and neutralizes gastric acid to achieve a sustained release and continuous treatment of the stomach and duodenum.
- Step (1) Raw material processing: the raw and auxiliary hydrotalcite, filler and disintegrant in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, drug delivery rate regulator, gastric floating additive, foaming agent, expander and hydrophilic gel in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;
- Step (2) preparing mixed powder: placing the raw materials of the common layer of aluminum carbonate, aluminum carbonate, filler and disintegrant in a three-dimensional motion mixer and mixing for 10 minutes to obtain the total mixed powder 1 for tableting; adding the raw materials of the sustained-release layer of aluminum carbonate, aluminum carbonate, drug delivery rate regulator, gastric floating additive, foaming agent, expander and hydrophilic gel to the three-dimensional motion mixer and mixing for 15 minutes to obtain the total mixed powder 2 for tableting;
- Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.
- the filler in the common layer of hydrotalcite is lactose
- the disintegrant is low-substituted hydroxypropyl cellulose.
- aluminum carbonate is the main drug
- the administration rate regulator in the auxiliary materials is mannitol
- the gastric floating additive is stearic acid
- the swelling agent is gelatin
- the foaming agent is sodium carbonate
- the hydrophilic gel is HPMC.
- aluminum carbonate is 170 to 200 parts
- lactose is 60 to 77 parts
- low-substituted hydroxypropyl cellulose is 30 to 60 parts.
- hydrotalcite sustained-release layer of step (2) hydrotalcite is 50 to 80 parts, mannitol is 20 to 30 parts, stearic acid is 130 to 170 parts, sodium carbonate is 80 to 150 parts, and The glue is 85-105 parts, and the HPMC is 30-60 parts.
- a method for preparing a hydrotalcite double-layer tablet is carried out according to the following steps:
- Step (1) Raw material processing: the raw and auxiliary hydrotalcite, lactose and low-substituted hydroxyl in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, mannitol, stearic acid, gelatin, sodium carbonate and HPMC in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;
- Step (2) preparing a mixed powder: according to the weight percentage, 170-200 parts of the raw materials of the normal layer of the sieved aluminum carbonate, 60-77 parts of lactose, and 30-60 parts of low-substituted hydroxypropyl cellulose are placed in a three-dimensional motion mixer and mixed for 10 minutes to obtain a total mixed powder 1 for tableting; 50-80 parts of the raw materials of the sustained-release layer of the sieved aluminum carbonate, 30-40 parts of mannitol, 130-170 parts of stearic acid, 80-150 parts of sodium carbonate, 85-105 parts of gelatin, and 30-60 parts of HPMC are added to a three-dimensional motion mixer and mixed for 15 minutes to obtain a total mixed powder 2 for tableting;
- Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.
- the aluminum carbonate magnesium double-layer tablet prepared by the present invention has a rapid onset of treatment for gastric and duodenal ulcers, is more durable, and has better patient compliance.
- the stability test results show that the stability is within 24 months, and the main drug content of the common layer and the sustained-release layer of the product hardly changes.
- the common layer of the aluminum carbonate magnesium double-layer tablet can be completely peeled off from the sustained-release layer and sink into the lower layer in about 30 seconds, quickly neutralizes gastric acid, and takes effect quickly.
- the release time of the sustained-release layer after forming a floating layer is as long as 4 hours, which proves that the aluminum carbonate magnesium double-layer tablet has a sustained-release effect within 4 hours after administration, and can effectively prolong the treatment time of patients with gastric ulcers and duodenal ulcers.
- the preparation method is simple and feasible and is worthy of promotion.
- a method for preparing a hydrotalcite double-layer tablet is carried out according to the following steps:
- Step (1) Raw material processing: the raw and auxiliary hydrotalcite, lactose and low-substituted hydroxyl in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, mannitol, stearic acid, gelatin, sodium carbonate and HPMC in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;
- Step (2) preparing a mixed powder: according to the weight percentage, 200 parts of the raw materials of the normal layer of the sieved aluminum carbonate, 60 parts of lactose, and 50 parts of low-substituted hydroxypropyl cellulose are placed in a three-dimensional motion mixer and mixed for 10 minutes to obtain a total mixed powder 1 for tableting; 50 parts of the raw materials of the sustained-release layer of the sieved aluminum carbonate, 20 parts of mannitol, 140 parts of stearic acid, 80 parts of sodium carbonate, 100 parts of gelatin, and 30 parts of HPMC are added to a three-dimensional motion mixer and mixed for 15 minutes to obtain a total mixed powder 2 for tableting;
- Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.
- a method for preparing a hydrotalcite double-layer tablet is carried out according to the following steps:
- Step (1) Raw material processing: the raw and auxiliary hydrotalcite, lactose and low-substituted hydroxyl in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, mannitol, stearic acid, gelatin, sodium carbonate and HPMC in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;
- Step (2) preparing a mixed powder: according to the weight percentage, 170 parts of the raw materials of the ordinary layer of the sieved aluminum carbonate, 77 parts of lactose, and 30 parts of low-substituted hydroxypropyl cellulose are placed in a three-dimensional motion mixer and mixed for 10 minutes to obtain a total mixed powder 1 for tableting; 80 parts of the raw materials of the sustained-release layer of the sieved aluminum carbonate, 30 parts of mannitol, 170 parts of stearic acid, 150 parts of sodium carbonate, 85 parts of gelatin, and 60 parts of HPMC are added to a three-dimensional motion mixer and mixed for 15 minutes to obtain a total mixed powder 2 for tableting;
- Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.
- a method for preparing a hydrotalcite double-layer tablet is carried out according to the following steps:
- Step (1) Raw material processing: the raw and auxiliary hydrotalcite, lactose and low-substituted hydroxyl in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, mannitol, stearic acid, gelatin, sodium carbonate and HPMC in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;
- Step (2) preparing a mixed powder: according to the weight percentage, 180 parts of the raw materials of the normal layer of the sieved aluminum carbonate, 70 parts of lactose, and 60 parts of low-substituted hydroxypropyl methylcellulose are placed in a three-dimensional motion mixer and mixed for 10 minutes to obtain a total mixed powder 1 for tableting; 70 parts of the raw materials of the sustained-release layer of the sieved aluminum carbonate, 25 parts of mannitol, 130 parts of stearic acid, 100 parts of sodium carbonate, 105 parts of gelatin, and 50 parts of HPMC are added to a three-dimensional motion mixer and mixed for 15 minutes to obtain a total mixed powder 2 for tableting;
- Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.
- hydrotalcite bilayer tablets prepared by the present invention were subjected to dissolution test and long-term stability test.
- Test method Refer to the stability test of Part II of the 2020 edition of the Chinese Pharmacopoeia
- Dissolution curve test was performed on the retained samples at 0, 1, 2, 3, and 6 months under the condition of pH 1.2 to observe the change of dissolution rate.
- Dissolution test method The aluminum carbonate magnesium bilayer tablets prepared in Examples 1, 2, and 3 were tested for dissolution curves. The test method was based on the first method of the 2020 edition of the Pharmacopoeia Standard Operating Procedure, with 1000 ml of pH 1.2 salt buffer as the release medium, and the rotation speed was 100 turns per min. The blue method was operated according to the law. 5 ml of solution was taken after 5 min, 10 min, 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, 180 min, 240 min, 300 min, and 360 min, respectively, and filtered.
- Example 2 Compared with Example 1, in the raw materials of the hydrotalcite sustained-release layer, sodium carbonate was replaced with an equal amount of lactose, and the other components remained unchanged.
- the acid-suppressing power of the aluminum carbonate bilayer tablet prepared in comparative example 1 is 326.4 mL.
- the aluminum carbonate bilayer tablet prepared in comparative example 1 is separated from the ordinary layer and the sustained-release layer at 30 seconds, and the ordinary layer is completely disintegrated.
- a small amount of bubbles are generated when the artificial gastric juice is just put into the artificial gastric juice.
- the aluminum carbonate sustained-release layer is opened, the diffuse powder gradually sinks to the bottom of the bottle.
- the sustained-release layer swims in the bottle without direction, and the surrounding bubbles do not change much.
- the sustained-release layer slowly sinks after floating for about 30 seconds, and the tablet gradually becomes smaller.
- Example 2 Compared with Example 1, the gelatin in the raw material of the hydrotalcite sustained-release layer of hydrotalcite was replaced with an equal amount of lactose, and the other components remained unchanged.
- the acid antacidity of the aluminum carbonate magnesium bilayer tablet prepared in Comparative Example 2 was 331.9 mL.
- the ordinary layer and the sustained-release layer of the aluminum carbonate magnesium bilayer tablet prepared in Comparative Example 2 were separated at 38 s, and the ordinary layer was completely disintegrated. A small amount of bubbles are generated when the artificial gastric juice is just put into the bottle. After the aluminum carbonate sustained-release layer pops up, the diffused powder gradually sinks to the bottom of the bottle.
- the sustained-release layer swims in the bottle without direction, and the number of bubbles around it increases, floating in the beaker, but the floating time is short, only maintaining 42 seconds, and then slowly sinking, the sinking speed is slightly slower than that of comparative example 1.
- the sustained-release layer tablets gradually become smaller. Due to the absence of gelatin to promote the expansion of the hydrogel, the dissolution of the mannitol and lactose inside is hindered, and the reaction of sodium carbonate with acid is slow, making the sustained release of the drug difficult. At 290 minutes, the floating sustained-release layer completely disintegrates.
- Such a sustained-release rate causes the aluminum carbonate in the sustained-release layer to be unable to connect with the efficacy of the aluminum carbonate in the ordinary layer, resulting in a fault, and the amount of aluminum carbonate in the sustained-release layer is small, and it cannot independently exert a more obvious efficacy.
- the aluminum carbonate magnesium double-layer tablet prepared by the present invention takes a shorter time to reach pH 3, which can achieve the purpose of rapid onset of effect, and maintains pH 3-5 for a longer time, which can achieve a long-term anti-acid effect.
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Abstract
Description
本发明涉及制药技术领域，具体涉及一种铝碳酸镁双层片及其制备方法。The invention relates to the technical field of pharmaceuticals, and in particular to a hydrotalcite double-layer tablet and a preparation method thereof.
铝碳酸镁颗粒是一种用于急、慢性胃炎、胃溃疡、十二指肠溃疡、返流性食管炎、与胃酸有关的胃部不适症状，如胃痛、胃灼热、酸性嗳气、饱胀，预防非甾体类药物引起的胃粘膜损伤等的药物。目前市场上有铝碳酸镁颗粒、铝碳酸镁混悬液、铝碳酸镁咀嚼片、铝碳酸镁共干凝胶4种剂型，其中铝碳酸镁颗粒、片剂、铝碳酸镁共干凝胶为普通产品，原理基本一致，缺点是在胃内滞留时间不长，要么快速缓释，快速产生效果，但是时效较短，要么药物缓释较慢，时效长，但是起效慢，药效不明显，即不能同时达到及时治疗和长效保持治疗效果的作用。Aluminum carbonate granules are a drug used for acute and chronic gastritis, gastric ulcer, duodenal ulcer, reflux esophagitis, stomach discomfort symptoms related to gastric acid, such as stomach pain, heartburn, acidic belching, fullness, prevention of gastric mucosal damage caused by non-steroidal drugs, etc. At present, there are four dosage forms of aluminum carbonate granules, aluminum carbonate suspension, aluminum carbonate chewable tablets, and aluminum carbonate co-dry gel on the market. Among them, aluminum carbonate granules, tablets, and aluminum carbonate co-dry gel are common products with basically the same principle. The disadvantage is that the retention time in the stomach is not long. Either the drug is released quickly and the effect is produced quickly, but the time effect is short, or the drug is released slowly and the time effect is long, but the onset is slow and the drug effect is not obvious, that is, it cannot achieve the effect of timely treatment and long-term maintenance of the therapeutic effect at the same time.
发明内容Summary of the invention
本发明目的在于提供一种铝碳酸镁双层片。The present invention aims to provide a hydrotalcite double-layer tablet.
本发明另一目的在于提供一种铝碳酸镁双层片的制备方法，通过解决了双层片结构中面临的均匀性差，普通层与缓释层对于铝碳酸镁的释放紊乱的问题，使得铝碳酸镁双层片达到及时治疗和长效保持治疗效果的作用。Another object of the present invention is to provide a method for preparing a hydrotalcite double-layer tablet, which solves the problems of poor uniformity in the double-layer tablet structure and disordered release of hydrotalcite between the ordinary layer and the sustained-release layer, so that the hydrotalcite double-layer tablet can achieve the effect of timely treatment and long-term maintenance of the therapeutic effect.
本发明目的通过如下技术方案实现：The purpose of the present invention is achieved through the following technical solutions:
一种铝碳酸镁双层片，其特征在于，所述双层片是由一层铝碳酸镁普通层和一层铝碳酸镁缓释层压制得到，所述碳酸铝镁普通层中，铝碳酸镁为主药，辅料为填充剂和崩解剂，所述碳酸铝镁缓释层中，主药为铝碳酸镁，辅料为给药速率调节剂、胃漂浮附加剂、膨胀剂、发泡剂和亲水凝胶。A double-layer aluminum carbonate tablet, characterized in that the double-layer tablet is obtained by pressing a common aluminum carbonate layer and a sustained-release aluminum carbonate layer, wherein the common aluminum carbonate layer contains aluminum carbonate as the main drug, and the auxiliary materials are fillers and disintegrants, and the sustained-release aluminum carbonate layer contains aluminum carbonate as the main drug, and the auxiliary materials are administration rate regulators, gastric floating additives, expanders, foaming agents and hydrophilic gels.
进一步，所述填充剂包括乳糖、甘露醇、微晶纤维素中的一种或多种。Furthermore, the filler includes one or more of lactose, mannitol, and microcrystalline cellulose.
进一步，所述崩解剂为低取代羟甲基纤维素、羧甲基淀粉钠中的一种或多种。Furthermore, the disintegrant is one or more of low-substituted hydroxymethyl cellulose and sodium carboxymethyl starch.
进一步，所述给药速率调节剂为乳糖和甘露醇中一种或多种。 Furthermore, the administration rate regulator is one or more of lactose and mannitol.
进一步，所述胃漂浮附加剂包括单硬脂酸甘油酯、十八烷醇、硬脂酸和蜂蜡中的一种或多种。Furthermore, the gastric floating additive includes one or more of glyceryl monostearate, stearyl alcohol, stearic acid and beeswax.
进一步，所述膨胀剂为明胶、阿拉伯胶中的一种或多种。Furthermore, the swelling agent is one or more of gelatin and gum arabic.
进一步，所述发泡剂为碳酸钠、碳酸氢钠中任意一种。Furthermore, the foaming agent is any one of sodium carbonate and sodium bicarbonate.
进一步，所述亲水凝胶包括羟丙甲基纤维素(HPMC)、羧甲基纤维素钠(CMC-Na)、聚乙烯吡咯烷酮(PVP)和聚乙烯醇(PVA)中的一种或多种。Furthermore, the hydrophilic gel includes one or more of hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (CMC-Na), polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA).
进一步，按照质量份数计，所述铝碳酸镁普通层中，铝碳酸镁为150～200份，填充剂为60～77份，崩解剂为30～60份。Furthermore, in terms of weight percentage, in the common hydrotalcite layer, hydrotalcite is present in an amount of 150 to 200 parts, filler is present in an amount of 60 to 77 parts, and disintegrant is present in an amount of 30 to 60 parts.
进一步，按照质量份数计，所述铝碳酸镁缓释层中，铝碳酸镁为50～80份，给药速率调节剂为20～30份，胃漂浮附加剂为130～170份，发泡剂为80～150份，膨胀剂为85～105份，亲水凝胶为30～60份。Furthermore, in terms of weight percentage, in the aluminum carbonate sustained-release layer, aluminum carbonate is 50 to 80 parts, the administration rate regulator is 20 to 30 parts, the gastric floating additive is 130 to 170 parts, the foaming agent is 80 to 150 parts, the expander is 85 to 105 parts, and the hydrophilic gel is 30 to 60 parts.
优选地，所述碳酸镁铝普通层中，辅料中填充剂为乳糖，崩解剂为低取代羟丙基纤维素。Preferably, in the common layer of magnesium aluminum carbonate, the filler in the auxiliary materials is lactose, and the disintegrant is low-substituted hydroxypropyl cellulose.
优选地，所述碳酸镁铝缓释层中铝碳酸镁为主药，辅料中给药速率调节剂为甘露醇，胃漂浮附加剂为硬脂酸、膨胀剂为明胶、发泡剂为碳酸钠、亲水凝胶为HPMC。Preferably, in the aluminum carbonate sustained-release layer, aluminum carbonate is the main drug, the administration rate regulator in the auxiliary materials is mannitol, the gastric floating additive is stearic acid, the swelling agent is gelatin, the foaming agent is sodium carbonate, and the hydrophilic gel is HPMC.
进一步，按照质量份数计，所述铝碳酸镁普通层中，铝碳酸镁为170～200份，乳糖为60～77份，低取代羟丙基纤维素为30～60份。Furthermore, in terms of weight percentage, in the ordinary hydrotalcite layer, hydrotalcite is present in an amount of 170 to 200 parts, lactose is present in an amount of 60 to 77 parts, and low-substituted hydroxypropyl cellulose is present in an amount of 30 to 60 parts.
进一步，按照质量份数计，所述铝碳酸镁缓释层中，铝碳酸镁为50～80份，甘露醇为20～30份，硬脂酸为130～170份，碳酸钠为80～150份，明胶为85～105份，HPMC为30～60份。Furthermore, in terms of weight percentage, in the hydrotalcite sustained-release layer, hydrotalcite is 50-80 parts, mannitol is 20-30 parts, stearic acid is 130-170 parts, sodium carbonate is 80-150 parts, gelatin is 85-105 parts, and HPMC is 30-60 parts.
本发明的铝碳酸镁双层片治疗胃溃疡、十二指长溃疡基本原理是铝碳酸镁普通层遇到胃液时在崩解剂低取代羟丙基纤维素作用下迅速崩解与铝碳酸镁缓释层产生剥离，同时，铝碳酸镁缓释层中明胶遇胃液后在亲水凝胶羟丙甲基纤维素作用下体积迅速膨胀，在铝碳酸镁普通层崩解和缓释层中明胶的膨胀的双重作用下，缓释层从铝碳酸镁普通层表面迅速脱落，普通层在铝碳酸镁重力作用下下沉粘附在胃表面，快速起效保护胃黏膜不被胃酸浸蚀，铝碳酸镁与胃酸 反应产生气体形成助推力，反向推动铝碳酸镁缓释层在胃部不定向游走，使得缓释层能在胃部不同位置释放药物。游走状态的缓释层中的甘露醇/乳糖遇水后均匀溶解，在缓释层表面形成一定的均匀分布的孔隙，使得胃酸与发泡剂碳酸钠充分接触，反应产生二氧化碳，二氧化碳气体与硬脂酸协同使得缓释层可以长时间漂浮在胃中，形成胃漂浮片，使得反应生成的二氧化碳在缓释层中的均匀穿梭，进一步将甘露醇溶解生成的孔隙贯穿形成孔洞，形成缓释通道，调节了缓释层中铝碳酸镁的释放速率，达到了持续缓慢释放铝碳酸镁成份，中和胃酸达到缓释持续治疗胃、十二肠作用。The basic principle of the aluminum carbonate double-layer tablet for treating gastric ulcer and duodenal ulcer is that when the ordinary layer of aluminum carbonate encounters gastric juice, it quickly disintegrates under the action of the disintegrant low-substituted hydroxypropyl cellulose and is peeled off from the sustained-release layer of aluminum carbonate. At the same time, the gelatin in the sustained-release layer of aluminum carbonate rapidly expands in volume under the action of the hydrophilic gel hydroxypropyl methylcellulose after encountering gastric juice. Under the dual effects of the disintegration of the ordinary layer of aluminum carbonate and the expansion of the gelatin in the sustained-release layer, the sustained-release layer quickly falls off from the surface of the ordinary layer of aluminum carbonate, and the ordinary layer sinks and adheres to the stomach surface under the gravity of aluminum carbonate, quickly takes effect to protect the gastric mucosa from being eroded by gastric acid, and aluminum carbonate and gastric acid The reaction generates gas to form a boosting force, which pushes the aluminum carbonate sustained-release layer in the stomach in an undirected manner, so that the sustained-release layer can release drugs at different positions in the stomach. The mannitol/lactose in the sustained-release layer in the wandering state dissolves evenly after meeting water, forming certain evenly distributed pores on the surface of the sustained-release layer, so that gastric acid and the foaming agent sodium carbonate are fully in contact, and the reaction generates carbon dioxide. The carbon dioxide gas and stearic acid cooperate to allow the sustained-release layer to float in the stomach for a long time, forming a gastric floating tablet, so that the carbon dioxide generated by the reaction shuttles evenly in the sustained-release layer, further penetrates the pores generated by the dissolution of mannitol to form holes, and forms a sustained-release channel, which regulates the release rate of aluminum carbonate in the sustained-release layer, achieves a continuous and slow release of the aluminum carbonate component, and neutralizes gastric acid to achieve a sustained release and continuous treatment of the stomach and duodenum.
一种铝碳酸镁双层片的制备方法，其特征在于，按如下步骤进行：A method for preparing a hydrotalcite double-layer tablet is characterized by comprising the following steps:
步骤(1)原料处理：铝碳酸镁普通层中的原辅铝碳酸镁、填充剂和崩解剂分别过100目筛备用；将铝碳酸镁缓释层中的原料铝碳酸镁、给药速率调节剂、胃漂浮附加剂、发泡剂、膨胀剂和亲水凝胶分别过200目筛备用；Step (1) Raw material processing: the raw and auxiliary hydrotalcite, filler and disintegrant in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, drug delivery rate regulator, gastric floating additive, foaming agent, expander and hydrophilic gel in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;
步骤(2)制备混粉：将铝碳酸镁普通层的原料铝碳酸镁、填充剂和崩解剂置于三维运动混合机中，混合10min，作为压片的总混粉1，将铝碳酸镁缓释层的原料铝碳酸镁、给药速率调节剂、胃漂浮附加剂、发泡剂、膨胀剂和亲水凝胶加入三维运动混合机中总混15min，为压片总混粉2；Step (2) preparing mixed powder: placing the raw materials of the common layer of aluminum carbonate, aluminum carbonate, filler and disintegrant in a three-dimensional motion mixer and mixing for 10 minutes to obtain the total mixed powder 1 for tableting; adding the raw materials of the sustained-release layer of aluminum carbonate, aluminum carbonate, drug delivery rate regulator, gastric floating additive, foaming agent, expander and hydrophilic gel to the three-dimensional motion mixer and mixing for 15 minutes to obtain the total mixed powder 2 for tableting;
步骤(3)将总混颗粒1和总混颗粒2分别加入旋转压片机两个漏斗中，硬度控制在3～6kg，压片即得。Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.
进一步，所述步骤(1)中铝碳酸镁普通层中的填充剂为乳糖，崩解剂为低取代羟丙基纤维素。Furthermore, in the step (1), the filler in the common layer of hydrotalcite is lactose, and the disintegrant is low-substituted hydroxypropyl cellulose.
进一步，所述步骤(1)碳酸镁铝缓释层中铝碳酸镁为主药，辅料中给药速率调节剂为甘露醇，胃漂浮附加剂为硬脂酸、膨胀剂为明胶、发泡剂为碳酸钠、亲水凝胶为HPMC。Furthermore, in the step (1) of the aluminum carbonate sustained-release layer, aluminum carbonate is the main drug, the administration rate regulator in the auxiliary materials is mannitol, the gastric floating additive is stearic acid, the swelling agent is gelatin, the foaming agent is sodium carbonate, and the hydrophilic gel is HPMC.
进一步，按照质量份数计，所述步骤(2)铝碳酸镁普通层中，铝碳酸镁为170～200份，乳糖为60～77份，低取代羟丙基纤维素为30～60份。Furthermore, in terms of weight percentages, in the ordinary layer of aluminum carbonate in step (2), aluminum carbonate is 170 to 200 parts, lactose is 60 to 77 parts, and low-substituted hydroxypropyl cellulose is 30 to 60 parts.
进一步，按照质量份数计，所述步骤(2)铝碳酸镁缓释层中，铝碳酸镁为50～80份，甘露醇为20～30份，硬脂酸为130～170份，碳酸钠为80～150份，明 胶为85～105份，HPMC为30～60份。Further, in terms of weight parts, in the hydrotalcite sustained-release layer of step (2), hydrotalcite is 50 to 80 parts, mannitol is 20 to 30 parts, stearic acid is 130 to 170 parts, sodium carbonate is 80 to 150 parts, and The glue is 85-105 parts, and the HPMC is 30-60 parts.
最具体地，一种铝碳酸镁双层片的制备方法，按如下步骤进行：Most specifically, a method for preparing a hydrotalcite double-layer tablet is carried out according to the following steps:
步骤(1)原料处理：铝碳酸镁普通层中的原辅铝碳酸镁、乳糖和低取代羟分别过100目筛备用；将铝碳酸镁缓释层中的原料铝碳酸镁、甘露醇、硬脂酸、明胶、碳酸钠和HPMC分别过200目筛备用；Step (1) Raw material processing: the raw and auxiliary hydrotalcite, lactose and low-substituted hydroxyl in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, mannitol, stearic acid, gelatin, sodium carbonate and HPMC in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;
步骤(2)制备混粉：按照质量份数计，将过筛后的铝碳酸镁普通层的原料铝碳酸镁为170～200份，乳糖为60～77，低取代羟丙基纤维素为30～60份置于三维运动混合机中，混合10min，作为压片的总混粉1，将过筛后的铝碳酸镁缓释层的原料铝碳酸镁为50～80份，甘露醇为30～40份，硬脂酸为130～170份，碳酸钠为80～150份，明胶为85～105份，HPMC为30～60份加入三维运动混合机中总混15min，为压片总混粉2；Step (2) preparing a mixed powder: according to the weight percentage, 170-200 parts of the raw materials of the normal layer of the sieved aluminum carbonate, 60-77 parts of lactose, and 30-60 parts of low-substituted hydroxypropyl cellulose are placed in a three-dimensional motion mixer and mixed for 10 minutes to obtain a total mixed powder 1 for tableting; 50-80 parts of the raw materials of the sustained-release layer of the sieved aluminum carbonate, 30-40 parts of mannitol, 130-170 parts of stearic acid, 80-150 parts of sodium carbonate, 85-105 parts of gelatin, and 30-60 parts of HPMC are added to a three-dimensional motion mixer and mixed for 15 minutes to obtain a total mixed powder 2 for tableting;
步骤(3)将总混颗粒1和总混颗粒2分别加入旋转压片机两个漏斗中，硬度控制在3～6kg，压片即得。Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.
本发明具有如下技术效果：The present invention has the following technical effects:
本发明制得的铝碳酸镁双层片对胃、十二指肠溃疡的治疗起效快的同时，更加持久、患者的顺应性更好，经稳定性试验结果表明稳定性在24月内，产品普通层和缓释层的主药含量几乎不发生改变，铝碳酸镁双层片的普通层在30s左右可从缓释层完全剥离开来沉入下层，迅速中和胃酸，迅速起效，同时，缓释层形成漂浮层后释放时间长达4h，证明铝碳酸镁双层片在用药后的4h内有缓释作用，能有效延长胃溃疡、十二指肠溃疡患者的治疗时间，此制备方法简单可行，值得推广。The aluminum carbonate magnesium double-layer tablet prepared by the present invention has a rapid onset of treatment for gastric and duodenal ulcers, is more durable, and has better patient compliance. The stability test results show that the stability is within 24 months, and the main drug content of the common layer and the sustained-release layer of the product hardly changes. The common layer of the aluminum carbonate magnesium double-layer tablet can be completely peeled off from the sustained-release layer and sink into the lower layer in about 30 seconds, quickly neutralizes gastric acid, and takes effect quickly. At the same time, the release time of the sustained-release layer after forming a floating layer is as long as 4 hours, which proves that the aluminum carbonate magnesium double-layer tablet has a sustained-release effect within 4 hours after administration, and can effectively prolong the treatment time of patients with gastric ulcers and duodenal ulcers. The preparation method is simple and feasible and is worthy of promotion.
下面通过实施例对本发明进行具体的描述，不能理解为对本发明保护范围的限制，该领域的技术人员可以根据上述本发明内容对本发明作出一些非本质的改进和调整。The present invention is described in detail below through embodiments, which should not be construed as limiting the protection scope of the present invention. Those skilled in the art can make some non-essential improvements and adjustments to the present invention based on the above contents of the present invention.
实施例1Example 1
一种铝碳酸镁双层片的制备方法，按如下步骤进行： A method for preparing a hydrotalcite double-layer tablet is carried out according to the following steps:
步骤(1)原料处理：铝碳酸镁普通层中的原辅铝碳酸镁、乳糖和低取代羟分别过100目筛备用；将铝碳酸镁缓释层中的原料铝碳酸镁、甘露醇、硬脂酸、明胶、碳酸钠和HPMC分别过200目筛备用；Step (1) Raw material processing: the raw and auxiliary hydrotalcite, lactose and low-substituted hydroxyl in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, mannitol, stearic acid, gelatin, sodium carbonate and HPMC in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;
步骤(2)制备混粉：按照质量份数计，将过筛后的铝碳酸镁普通层的原料铝碳酸镁为200份，乳糖为60，低取代羟丙基纤维素为50份置于三维运动混合机中，混合10min，作为压片的总混粉1，将过筛后的铝碳酸镁缓释层的原料铝碳酸镁为50份，甘露醇为20份，硬脂酸为140份，碳酸钠为80份，明胶为100份，HPMC为30份加入三维运动混合机中总混15min，为压片总混粉2；Step (2) preparing a mixed powder: according to the weight percentage, 200 parts of the raw materials of the normal layer of the sieved aluminum carbonate, 60 parts of lactose, and 50 parts of low-substituted hydroxypropyl cellulose are placed in a three-dimensional motion mixer and mixed for 10 minutes to obtain a total mixed powder 1 for tableting; 50 parts of the raw materials of the sustained-release layer of the sieved aluminum carbonate, 20 parts of mannitol, 140 parts of stearic acid, 80 parts of sodium carbonate, 100 parts of gelatin, and 30 parts of HPMC are added to a three-dimensional motion mixer and mixed for 15 minutes to obtain a total mixed powder 2 for tableting;
步骤(3)将总混颗粒1和总混颗粒2分别加入旋转压片机两个漏斗中，硬度控制在3～6kg，压片即得。Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.
实施例2Example 2
一种铝碳酸镁双层片的制备方法，按如下步骤进行：A method for preparing a hydrotalcite double-layer tablet is carried out according to the following steps:
步骤(1)原料处理：铝碳酸镁普通层中的原辅铝碳酸镁、乳糖和低取代羟分别过100目筛备用；将铝碳酸镁缓释层中的原料铝碳酸镁、甘露醇、硬脂酸、明胶、碳酸钠和HPMC分别过200目筛备用；Step (1) Raw material processing: the raw and auxiliary hydrotalcite, lactose and low-substituted hydroxyl in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, mannitol, stearic acid, gelatin, sodium carbonate and HPMC in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;
步骤(2)制备混粉：按照质量份数计，将过筛后的铝碳酸镁普通层的原料铝碳酸镁为170份，乳糖为77份，低取代羟丙基纤维素为30份置于三维运动混合机中，混合10min，作为压片的总混粉1，将过筛后的铝碳酸镁缓释层的原料铝碳酸镁为80份，甘露醇为30份，硬脂酸为170份，碳酸钠为150份，明胶为85份，HPMC为60份加入三维运动混合机中总混15min，为压片总混粉2；Step (2) preparing a mixed powder: according to the weight percentage, 170 parts of the raw materials of the ordinary layer of the sieved aluminum carbonate, 77 parts of lactose, and 30 parts of low-substituted hydroxypropyl cellulose are placed in a three-dimensional motion mixer and mixed for 10 minutes to obtain a total mixed powder 1 for tableting; 80 parts of the raw materials of the sustained-release layer of the sieved aluminum carbonate, 30 parts of mannitol, 170 parts of stearic acid, 150 parts of sodium carbonate, 85 parts of gelatin, and 60 parts of HPMC are added to a three-dimensional motion mixer and mixed for 15 minutes to obtain a total mixed powder 2 for tableting;
步骤(3)将总混颗粒1和总混颗粒2分别加入旋转压片机两个漏斗中，硬度控制在3～6kg，压片即得。Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.
实施例3Example 3
一种铝碳酸镁双层片的制备方法，按如下步骤进行：A method for preparing a hydrotalcite double-layer tablet is carried out according to the following steps:
步骤(1)原料处理：铝碳酸镁普通层中的原辅铝碳酸镁、乳糖和低取代羟分别过100目筛备用；将铝碳酸镁缓释层中的原料铝碳酸镁、甘露醇、硬脂酸、明胶、碳酸钠和HPMC分别过200目筛备用； Step (1) Raw material processing: the raw and auxiliary hydrotalcite, lactose and low-substituted hydroxyl in the hydrotalcite common layer are respectively passed through a 100-mesh sieve for later use; the raw materials hydrotalcite, mannitol, stearic acid, gelatin, sodium carbonate and HPMC in the hydrotalcite sustained-release layer are respectively passed through a 200-mesh sieve for later use;
步骤(2)制备混粉：按照质量份数计，将过筛后的铝碳酸镁普通层的原料铝碳酸镁为180份，乳糖为70份，低取代羟丙甲基纤维素为60份置于三维运动混合机中，混合10min，作为压片的总混粉1，将过筛后的铝碳酸镁缓释层的原料铝碳酸镁为70份，甘露醇为25份，硬脂酸为130份，碳酸钠为100份，明胶为105份，HPMC为50份加入三维运动混合机中总混15min，为压片总混粉2；Step (2) preparing a mixed powder: according to the weight percentage, 180 parts of the raw materials of the normal layer of the sieved aluminum carbonate, 70 parts of lactose, and 60 parts of low-substituted hydroxypropyl methylcellulose are placed in a three-dimensional motion mixer and mixed for 10 minutes to obtain a total mixed powder 1 for tableting; 70 parts of the raw materials of the sustained-release layer of the sieved aluminum carbonate, 25 parts of mannitol, 130 parts of stearic acid, 100 parts of sodium carbonate, 105 parts of gelatin, and 50 parts of HPMC are added to a three-dimensional motion mixer and mixed for 15 minutes to obtain a total mixed powder 2 for tableting;
步骤(3)将总混颗粒1和总混颗粒2分别加入旋转压片机两个漏斗中，硬度控制在3～6kg，压片即得。Step (3) Add the mixed granules 1 and 2 into two funnels of a rotary tablet press respectively, control the hardness to 3-6 kg, and compress the tablets to obtain the tablets.
实验一：Experiment 1:
用铝碳酸镁普通片和本发明制备的铝碳酸镁双层片进行人工胃液实验。Artificial gastric juice experiments were carried out using ordinary hydrotalcite tablets and the hydrotalcite double-layer tablets prepared by the present invention.
模拟人工胃液配制：Preparation of simulated artificial gastric juice:
1.将取浓度为1mol/mL的稀盐酸，加水稀释，将pH调至1.0，在2.5L溶液中加入25份胃蛋白酶，加入12.5份氯化钠和12.5份氯化钾，搅拌溶解完全后，用0.2um的无菌滤膜过滤得到模拟人工胃液。1. Take 1 mol/mL dilute hydrochloric acid, dilute with water, adjust the pH to 1.0, add 25 parts of pepsin, 12.5 parts of sodium chloride and 12.5 parts of potassium chloride to 2.5L solution, stir and dissolve completely, and filter with a 0.2um sterile filter membrane to obtain simulated artificial gastric juice.
2.将模拟人工胃液置于玻璃杯中，将玻璃杯放置在具有水浴保温系里、确保模拟人工滤液中的温度为37℃左右。2. Place the simulated artificial gastric juice in a glass cup, and place the glass cup in a water bath insulation system to ensure that the temperature of the simulated artificial filtrate is around 37°C.
3.取500mL pH为1.0模拟人工胃液加入在溶出杯中，加1片压制的铝碳酸双层片，调整搅拌转速为50转/min，搅拌观察现象，结果如表1所示：3. Take 500mL of simulated artificial gastric juice with a pH of 1.0 and add it to the dissolution cup. Add 1 compressed aluminum carbonate double-layer tablet, adjust the stirring speed to 50 rpm, stir and observe the phenomenon. The results are shown in Table 1:
表1：
Table 1:
实验二：Experiment 2:
将本发明制备的铝碳酸镁双层片进行溶出度试验和长期稳定性实验The hydrotalcite bilayer tablets prepared by the present invention were subjected to dissolution test and long-term stability test.
1.试验方法：参照2020年版《中国药典》第二部稳定性试验考察1. Test method: Refer to the stability test of Part II of the 2020 edition of the Chinese Pharmacopoeia
2.试验条件：2. Test conditions:
(1)溶出度曲线检测，在pH1.2的条件下在0月、1月、2月、3月、6月对留样样品进行溶出曲线检测，观察溶出度变化情况。(1) Dissolution curve test: Dissolution curve test was performed on the retained samples at 0, 1, 2, 3, and 6 months under the condition of pH 1.2 to observe the change of dissolution rate.
(2)长期试验温度：25±2℃；长期试验湿度：RH60％±10％(2) Long-term test temperature: 25±2℃; long-term test humidity: RH60%±10%
(3)长期试验考察时间：0、3、6、9、12、18、24月(3) Long-term test duration: 0, 3, 6, 9, 12, 18, 24 months
(4)溶出度试验考察时间:0、1、2、3、6(4) Dissolution test observation time: 0, 1, 2, 3, 6
(5)溶出试验方法：将实施例1、2、3制备的铝碳酸镁双层片进行溶出度曲线的检测，检测方法参照2020版药典标准操作程序第一法，以pH1.2的盐缓冲液1000ml为释放介质，转速为每min100转蓝法，依法操作，经5min、10min、15min、30min、45min、60min、90min、120min、180min、240min、300min，360min分别取溶液5mL，滤过，并即时在溶出杯中补充相同温度的pH1.2的盐酸缓冲液5mL；分别精密量取续滤液各1ml，置100mL量瓶中，用pH1.2的盐酸缓冲液稀释至刻度，摇匀，即得。测试得到的融出现曲线数据如表2所示。 (5) Dissolution test method: The aluminum carbonate magnesium bilayer tablets prepared in Examples 1, 2, and 3 were tested for dissolution curves. The test method was based on the first method of the 2020 edition of the Pharmacopoeia Standard Operating Procedure, with 1000 ml of pH 1.2 salt buffer as the release medium, and the rotation speed was 100 turns per min. The blue method was operated according to the law. 5 ml of solution was taken after 5 min, 10 min, 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, 180 min, 240 min, 300 min, and 360 min, respectively, and filtered. 5 ml of hydrochloric acid buffer at the same temperature was immediately added to the dissolution cup; 1 ml of the subsequent filtrate was accurately measured, placed in a 100 ml volumetric flask, diluted to the scale with hydrochloric acid buffer at pH 1.2, and shaken to obtain. The melting curve data obtained by the test are shown in Table 2.
表2：铝碳酸镁双层片的溶出曲线数据统计
Table 2: Dissolution curve statistics of hydrotalcite bilayer tablets
由上表溶出曲线数据可知，铝碳酸镁溶出10min，均可达到65％以上的溶出度，最高可达到80％以上，即可以达到迅速起效的作用，而10min后，双层片开始发挥缓慢释放效果，释放时间可到4h，即相对于普通的铝碳酸镁片、颗粒等，起到了缓慢释放的作用，延长药效，可减少服药次数，并且，放置6个月后，与0月相比，溶出行为未发生改变。It can be seen from the dissolution curve data in the above table that aluminum carbonate can reach a dissolution rate of more than 65% after dissolution for 10 minutes, and the highest can reach more than 80%, that is, it can achieve a rapid effect. After 10 minutes, the double-layer tablet begins to exert a slow release effect, and the release time can be up to 4 hours. That is, compared with ordinary aluminum carbonate magnesium tablets, granules, etc., it has a slow release effect, prolongs the efficacy, and can reduce the number of medications. Moreover, after 6 months, the dissolution behavior has not changed compared with 0 months.
实验三：长期制酸力、稳定性检测实验Experiment 3: Long-term acid-reducing capacity and stability test
取实施例1-3制备的铝碳酸镁双层片经盐酸滴定，取适量(约相当于铝碳酸镁0.5g)，精密称定，加少量水混合使成均匀的浆状，再加水使成100mL，精密加入盐酸滴定液(0.1mol/L)200mL，在37℃以每min200转的转速搅拌1h，测试每1g铝碳酸镁消耗盐酸滴定液(0.1mol/L)的量即为制酸力。具体制酸力 Take the aluminum carbonate double-layer tablets prepared in Example 1-3 and titrate them with hydrochloric acid. Take an appropriate amount (equivalent to about 0.5g of aluminum carbonate), accurately weigh it, add a small amount of water to mix it into a uniform slurry, then add water to make it 100mL, accurately add 200mL of hydrochloric acid titration solution (0.1mol/L), stir at 37℃ at a speed of 200 revolutions per minute for 1h, and test the amount of hydrochloric acid titration solution (0.1mol/L) consumed by every 1g of aluminum carbonate as the antacid capacity.
测试结果如表3所示。The test results are shown in Table 3.
表3：
Table 3:
备注：“--”表示未进行检测。 Note: "--" means no test was performed.
长期试验表明：本品实施例1、2、3长期试验24个月性状、鉴别、含量、微生物限度等各项指标均无显著变化，故本品长期试验24个月质量稳定。Long-term tests show that: the properties, identification, content, microbial limits and other indicators of Examples 1, 2 and 3 of the product have no significant changes in the 24-month long-term test, so the quality of this product is stable in the 24-month long-term test.
对比例1：Comparative Example 1:
与实施例1相比，铝碳酸镁缓释层原料中，将碳酸钠更换为等量的乳糖填充，其余组分不变。Compared with Example 1, in the raw materials of the hydrotalcite sustained-release layer, sodium carbonate was replaced with an equal amount of lactose, and the other components remained unchanged.
对比例1制备的铝碳酸镁双层片的制酸力为326.4mL，通过模拟人工胃液实验发现，对比例1制备的铝碳酸镁双层片在30s时，普通层与缓释层分离，且普通层完全崩解。刚投入人工胃液时有少量气泡产生，铝碳酸镁缓释层在弹开后，弥漫的粉末逐渐沉入瓶底，同时缓释层在瓶中无定向游动，且周围气泡变化不大，缓释层漂浮30s左右后缓慢下沉，片剂逐渐变小，由于没有碳酸钠与酸反应生成气体，形成缓释通道，而是依靠缓释层中明胶膨胀后，占比较大的甘露醇和乳糖溶于水，使得缓释层结构失稳而快速释放药物，在150min时，缓释层完全解体。The acid-suppressing power of the aluminum carbonate bilayer tablet prepared in comparative example 1 is 326.4 mL. Through the simulation of artificial gastric juice experiment, it is found that the aluminum carbonate bilayer tablet prepared in comparative example 1 is separated from the ordinary layer and the sustained-release layer at 30 seconds, and the ordinary layer is completely disintegrated. A small amount of bubbles are generated when the artificial gastric juice is just put into the artificial gastric juice. After the aluminum carbonate sustained-release layer is opened, the diffuse powder gradually sinks to the bottom of the bottle. At the same time, the sustained-release layer swims in the bottle without direction, and the surrounding bubbles do not change much. The sustained-release layer slowly sinks after floating for about 30 seconds, and the tablet gradually becomes smaller. Since there is no sodium carbonate reacting with the acid to generate gas to form a sustained-release channel, it depends on the expansion of gelatin in the sustained-release layer. The large proportion of mannitol and lactose dissolve in water, making the sustained-release layer structure unstable and quickly releasing drugs. At 150 minutes, the sustained-release layer completely disintegrates.
对比例2：Comparative Example 2:
与实施例1相比，铝碳酸镁中的铝碳酸镁缓释层原料中明胶替换成等量的乳糖填充，其余组分保持不变。Compared with Example 1, the gelatin in the raw material of the hydrotalcite sustained-release layer of hydrotalcite was replaced with an equal amount of lactose, and the other components remained unchanged.
对比例2制备的铝碳酸镁双层片的制酸力为331.9mL，通过模拟人工胃液实验发现，对比例2制备的铝碳酸镁双层片在38s时，普通层与缓释层分离，且普通层完全崩解。刚投入人工胃液时有少量气泡产生，铝碳酸镁缓释层在弹开后，弥漫的粉末逐渐沉入瓶底，同时缓释层在瓶中无定向游动，且周围气泡增多，漂浮在烧杯中，但是漂浮时间较短，仅仅维持了42s，开始缓慢下沉，下沉速度较对比例1稍慢，随着时间的推移，缓释层片剂逐渐变小，由于没有明胶促进水凝胶膨胀，使得内部的甘露醇、乳糖的溶解受阻，碳酸钠与酸的反应缓慢，使得药物的缓释困难，在290min时，浮缓释层完全解体，这样的缓释速率导致缓释层的中的铝碳酸镁能与普通层中的铝碳酸镁的药效无法衔接，出现断层，而缓释层中的铝碳酸镁量较少，无法独立发挥较明显的药效。The acid antacidity of the aluminum carbonate magnesium bilayer tablet prepared in Comparative Example 2 was 331.9 mL. Through the simulated artificial gastric juice experiment, it was found that the ordinary layer and the sustained-release layer of the aluminum carbonate magnesium bilayer tablet prepared in Comparative Example 2 were separated at 38 s, and the ordinary layer was completely disintegrated. A small amount of bubbles are generated when the artificial gastric juice is just put into the bottle. After the aluminum carbonate sustained-release layer pops up, the diffused powder gradually sinks to the bottom of the bottle. At the same time, the sustained-release layer swims in the bottle without direction, and the number of bubbles around it increases, floating in the beaker, but the floating time is short, only maintaining 42 seconds, and then slowly sinking, the sinking speed is slightly slower than that of comparative example 1. As time goes by, the sustained-release layer tablets gradually become smaller. Due to the absence of gelatin to promote the expansion of the hydrogel, the dissolution of the mannitol and lactose inside is hindered, and the reaction of sodium carbonate with acid is slow, making the sustained release of the drug difficult. At 290 minutes, the floating sustained-release layer completely disintegrates. Such a sustained-release rate causes the aluminum carbonate in the sustained-release layer to be unable to connect with the efficacy of the aluminum carbonate in the ordinary layer, resulting in a fault, and the amount of aluminum carbonate in the sustained-release layer is small, and it cannot independently exert a more obvious efficacy.
实验四：体外抗酸能力测试实验 Experiment 4: In vitro acid resistance test
根据Rossett rice体抗酸测试：将30mL水和70ml 0.1mol/L盐酸溶液加入反应容器中，用磁力加热搅拌器和接点温度计控制反应液处于37℃，磁力搅拌，搅拌速度为400r/min，测定反应容器内pH值的变化，恒流泵以(1±0.1)mL/min的速度向反应容器内泵入37℃恒温的0.1mol/L盐酸溶液。当加入实施例1-3和对比例1和2制备的铝碳酸镁双层片，立即开启恒流泵和磁力搅拌器，同时记录pH达到3的时间及保持时长。检测结果如表4所示。According to the Rossett rice body acid resistance test: 30mL water and 70ml 0.1mol/L hydrochloric acid solution are added to the reaction vessel, and the reaction solution is controlled at 37°C by a magnetic heating stirrer and a contact thermometer, and magnetic stirring is performed at a stirring speed of 400r/min. The change of pH value in the reaction vessel is measured, and a constant flow pump is pumped into the reaction vessel at a speed of (1±0.1)mL/min into the reaction vessel. 0.1mol/L hydrochloric acid solution at a constant temperature of 37°C. When the aluminum carbonate magnesium double-layer tablets prepared in Examples 1-3 and Comparative Examples 1 and 2 are added, the constant flow pump and magnetic stirrer are immediately turned on, and the time when pH reaches 3 and the duration of holding are recorded. The test results are shown in Table 4.
表4：
Table 4:
由上表可知，本发明制备的铝碳酸镁双层片达到pH为3的时间较短，可达到快速起效的目的，且保持pH为3～5的时间较长，可以达到长效抗酸的效果。 As can be seen from the above table, the aluminum carbonate magnesium double-layer tablet prepared by the present invention takes a shorter time to reach pH 3, which can achieve the purpose of rapid onset of effect, and maintains pH 3-5 for a longer time, which can achieve a long-term anti-acid effect.
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