CN114159399A - Oral cavity micro-bubble buccal tablet and preparation method thereof - Google Patents
Oral cavity micro-bubble buccal tablet and preparation method thereof Download PDFInfo
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- CN114159399A CN114159399A CN202111332516.2A CN202111332516A CN114159399A CN 114159399 A CN114159399 A CN 114159399A CN 202111332516 A CN202111332516 A CN 202111332516A CN 114159399 A CN114159399 A CN 114159399A
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- 239000006189 buccal tablet Substances 0.000 title claims abstract description 27
- 229940046011 buccal tablet Drugs 0.000 title claims abstract description 24
- 210000000214 mouth Anatomy 0.000 title claims description 10
- 238000002360 preparation method Methods 0.000 title abstract description 17
- 239000002253 acid Substances 0.000 claims abstract description 123
- 239000003513 alkali Substances 0.000 claims abstract description 114
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 40
- 238000002156 mixing Methods 0.000 claims abstract description 33
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 30
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims abstract description 28
- 229940013618 stevioside Drugs 0.000 claims abstract description 28
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims abstract description 28
- 235000019202 steviosides Nutrition 0.000 claims abstract description 28
- 239000004376 Sucralose Substances 0.000 claims abstract description 24
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims abstract description 24
- 235000019408 sucralose Nutrition 0.000 claims abstract description 24
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims abstract description 20
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims abstract description 20
- 239000011668 ascorbic acid Substances 0.000 claims abstract description 20
- 229960005070 ascorbic acid Drugs 0.000 claims abstract description 20
- 235000010323 ascorbic acid Nutrition 0.000 claims abstract description 20
- 239000000600 sorbitol Substances 0.000 claims abstract description 20
- 235000010356 sorbitol Nutrition 0.000 claims abstract description 20
- 229960004543 anhydrous citric acid Drugs 0.000 claims abstract description 12
- 239000000845 maltitol Substances 0.000 claims abstract description 12
- 235000010449 maltitol Nutrition 0.000 claims abstract description 12
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims abstract description 12
- 229940035436 maltitol Drugs 0.000 claims abstract description 12
- 239000000905 isomalt Substances 0.000 claims abstract description 11
- 235000010439 isomalt Nutrition 0.000 claims abstract description 11
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 claims abstract description 11
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 claims abstract description 9
- 239000000463 material Substances 0.000 claims description 68
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 56
- 238000000034 method Methods 0.000 claims description 30
- 235000019359 magnesium stearate Nutrition 0.000 claims description 28
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 15
- 239000011975 tartaric acid Substances 0.000 claims description 15
- 235000002906 tartaric acid Nutrition 0.000 claims description 15
- 239000004615 ingredient Substances 0.000 claims description 6
- SERLAGPUMNYUCK-YJOKQAJESA-N 6-O-alpha-D-glucopyranosyl-D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-YJOKQAJESA-N 0.000 claims 5
- 239000003826 tablet Substances 0.000 abstract description 42
- 238000004519 manufacturing process Methods 0.000 abstract description 23
- 238000010521 absorption reaction Methods 0.000 abstract description 8
- 238000012545 processing Methods 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 6
- 238000013068 supply chain management Methods 0.000 abstract description 3
- 239000000796 flavoring agent Substances 0.000 abstract description 2
- 235000019634 flavors Nutrition 0.000 abstract description 2
- 238000012423 maintenance Methods 0.000 abstract description 2
- 230000002035 prolonged effect Effects 0.000 abstract description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 abstract 1
- 239000010410 layer Substances 0.000 description 112
- 238000005303 weighing Methods 0.000 description 11
- 238000009472 formulation Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 238000007873 sieving Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000007938 effervescent tablet Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000003825 pressing Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000007910 chewable tablet Substances 0.000 description 2
- 229960004106 citric acid Drugs 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000428 dust Substances 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- HLLSOEKIMZEGFV-UHFFFAOYSA-N 4-(dibutylsulfamoyl)benzoic acid Chemical compound CCCCN(CCCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 HLLSOEKIMZEGFV-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 238000010670 acid alkali reaction Methods 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- -1 buccal patches Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000000003 vaginal tablet Substances 0.000 description 1
Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0007—Effervescent
-
- 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
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- 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
- A61K9/2009—Inorganic compounds
-
- 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
-
- 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
- A61K9/2072—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
-
- 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
Abstract
An oral micro-bubble buccal tablet belongs to the technical field of preparation of micro-bubble buccal tablets based on acid sources and alkali sources, wherein an acid source layer is mainly prepared from isomalt/maltitol, anhydrous citric acid and an acid source layer of sucralose/acid source layer of stevioside. The alkali source layer is mainly prepared from sorbitol, sodium bicarbonate, ascorbic acid and an alkali source layer of sucralose/stevioside. The preparation method comprises the following steps: and respectively mixing the acid source layer and the alkali source layer, and performing layering and tabletting. The multilayer tablet can ensure that the contact time of two incompatible raw materials is reduced to the maximum extent in the preparation process, so that the technical problem of easy moisture absorption of the preparation is solved, and the quality and flavor maintenance of the finished product after opening can be prolonged. The processing environment requirement is low, the production process is simple, and the supply chain management is flexible.
Description
Technical Field
The invention belongs to the technical field of preparation of micro-bubble buccal tablets based on acid sources and alkali sources, and particularly relates to an oral micro-bubble buccal tablet and a preparation method thereof.
Background
1. Low humidity processing environment requirements: the micro-bubble tablet processing process is different from the conventional tablet, the total mixed material is easy to absorb moisture due to the existence of an acid source and an alkali source, chemical reaction can occur in the material after moisture absorption, carbon dioxide and water are generated to further accelerate the moisture absorption and agglomeration of the whole material, and the chemical components of the material are changed, so the humidity of a clean area needs to be strictly controlled in the whole production process, and the RH is preferably less than or equal to 30%.
2. The fussy production process comprises the following steps: due to the existence of the acid source and the alkali source, the whole material powder has poor flowability, so the material needs to be granulated, the acid source and the alkali source need to be granulated and dried separately in order to prevent the acid source and the alkali source from generating chemical reaction in the granulating process, and meanwhile, the moisture in the dried material needs to be strictly controlled to prevent the acid source and the carbon source from generating reaction after subsequent mixing.
3. Difficult supply chain management: conventional micro-bubble tablets have high requirements on a supply chain, need to be prepared and used as the materials, and cannot be stored for a long time, so that the materials after total mixing need to be tabletted as soon as possible, which is not favorable for flexible management of the supply chain.
4. Strict finished product storage requirements: the micro-bubble pieces are sensitive to humidity, so that the unsealed product needs to be taken as soon as possible, and the influence of moisture absorption on the product sense is prevented.
5. The tablet is a tablet or special-shaped tablet solid preparation formed by uniformly mixing and pressing functional substances and auxiliary materials, the production process generally comprises the steps of crushing, mixing, granulating, drying and pressing the materials into tablets by a tablet press, and most of the tablets mainly comprise common oral tablets, and also comprise buccal tablets, sublingual tablets, buccal patches, chewable tablets, dispersible tablets, effervescent tablets, vaginal tablets, quick-release or sustained-release or controlled-release tablets, enteric-coated tablets and the like.
The micro-bubble tablet is similar to the effervescent tablet, and is a tablet prepared by compounding an acid source (generally citric acid, malic acid or tartaric acid and the like) and an alkali source (generally sodium bicarbonate), but the acid source and the alkali source are added in an amount which is adjusted to relieve the intensity of acid-alkali reaction, so that the micro-bubble carbon dioxide can be slowly released under the action of saliva in the oral cavity, and a delicate and innovative chewable tablet taste is produced.
Disclosure of Invention
The invention aims to provide an oral microbubble buccal tablet, and the invention also aims to provide a preparation method thereof, wherein an acid source and an alkali source are not directly contacted before a tabletting process, the requirement on humidity is low, and the product quality is good.
The technical scheme is as follows:
an oral micro-bubble buccal tablet comprises an acid source layer and an alkali source layer which are pressed and fixed.
The acid source layer is mainly prepared from 40-70 parts of isomalt (or maltitol), 10-25 parts of anhydrous citric acid (or tartaric acid), 0.1-0.3 part of sucralose (or stevioside) of the acid source layer), 0.5-2 parts of edible essence of the acid source layer and 1-2 parts of magnesium stearate of the acid source layer.
The alkali source layer is mainly prepared from 40-70 parts of sorbitol, 10-25 parts of sodium bicarbonate, 2-5 parts of ascorbic acid, 0.1-0.3 part of sucralose (or stevioside) in the alkali source layer, 0.5-2 parts of edible essence in the alkali source layer and 1-2 parts of magnesium stearate in the alkali source layer.
The parts are all parts by mass, and the edible essence is selected according to the required taste, and is the conventional technology in the field.
A method for preparing an oral cavity micro-bubble buccal tablet comprises the following steps: comprises the following steps:
1. preparing ingredients.
An acid source layer: 40-70 parts of isomalt (or maltitol), 10-25 parts of anhydrous citric acid (or tartaric acid), 0.1-0.3 part of sucralose (or stevioside) in an acid source layer), 0.5-2 parts of edible essence in the acid source layer and 1-2 parts of magnesium stearate in the acid source layer.
An alkali source layer: 40-70 parts of sorbitol, 10-25 parts of sodium bicarbonate, 2-5 parts of ascorbic acid, 0.1-0.3 part of sucralose (or stevioside) in an alkali source layer, 0.5-2 parts of edible essence in the alkali source layer and 1-2 parts of magnesium stearate in the alkali source layer.
2. And (3) mixing materials.
Preparing an acid source total mixed material: accurately weighing 40-70 parts of isomalt (or maltitol), 10-25 parts of anhydrous citric acid (or tartaric acid), 0.1-0.3 part of sucralose (or stevioside) and 0.5-2 parts of edible essence, namely materials except for magnesium stearate serving as an acid source layer, putting the materials into a three-dimensional mixer, mixing the materials at a rotating speed of 6-8 rpm for 20-40 min, adding 1-2 parts of magnesium stearate serving as the acid source layer, and mixing the materials for 5-15 min again to obtain the acid source material.
Preparing an alkali source total mixed material: accurately weighing 40-70 parts of sorbitol, 10-25 parts of sodium bicarbonate, 2-5 parts of ascorbic acid, 0.1-0.3 part of sucralose (or stevioside) in an alkali source layer and 0.5-2 parts of edible essence in the alkali source layer, namely the materials except magnesium stearate in the alkali source layer, putting the materials into a three-dimensional mixer, mixing the materials at the rotating speed of 6-8 rpm for 20-40 min, adding 1-2 parts of magnesium stearate in the alkali source layer, and mixing the materials for 5-15 min again to obtain the alkali source material.
3. And (5) layering and tabletting.
Adding the acid source material into the first layer of the filling hopper to start tabletting, and detecting the weight of the tablets to ensure that the difference of the weight of the tablets meets the requirement that the RSD value is less than or equal to 5 percent. Adding an alkali source material into the second layer of filler for tabletting, detecting the tablet weight to ensure that the difference of the tablet weight meets the requirement that the RSD value is less than or equal to 5 percent, and then pressing the two layers of the acid source layer and the alkali source layer together. (RSD is relative standard deviation).
The dust collection device of the tabletting machine is also connected in the specific operational process, so that the dust collection effect is observed, and the tabletting can be carried out when two materials cannot be mixed.
The new integration of the formulation technology and the preparation technology: the micro-bubble tablet is a novel tablet, but due to the particularity of the formula: the acid source and the alkali source are incompatible, and the humidity of the processing process and the moisture content of the materials need to be strictly controlled, so the requirement on the control of the production process is high, a production environment with low humidity is required, raw and auxiliary materials with low water activity and production raw materials need to be prepared for use on site, and meanwhile, the produced finished product is extremely easily influenced by the environment in the taking process (particularly in a plum rain high humidity environment and south China), and finally, a series of process problems of high production cost, complex process, high rejection rate, irreversibility and the like are caused. The multilayer tablet can ensure that the contact time of two incompatible raw materials is reduced to the greatest extent in the preparation process, so as to solve the technical problem of easy moisture absorption of the preparation, belongs to a novel combination of a formula technology and a preparation process, produces a microbubble tablet in a brand new state, and is a novel technical solution for solving the problem of difficult preparation of the microbubble tablet.
Interpretation of terms:
micro-bubble pieces: the novel effervescent tablet is a novel tablet between an effervescent tablet and a common tablet, the intensity of the reaction of an acid source (generally citric acid, malic acid or tartaric acid and the like) and an alkali source (generally sodium bicarbonate) is relieved by adjusting the adding amounts of the acid source and the alkali source, the inconvenience that the traditional effervescent tablet can be eaten only after an effervescent reaction occurs to water is effectively avoided, and simultaneously, a brand-new taking experience is brought by a mode of slowly releasing small bubbles in the oral cavity.
Multilayer sheet: refers to a tablet consisting of two or more layers.
The advantages are that:
the invention particularly relates to a processing mode of a production process of micro-bubble tablets, wherein an acid source and an alkali source are not directly contacted before a tabletting process, so that the sensitivity of the total mixed materials to humidity is reduced to the maximum extent, the humidity control of the whole workshop does not need to reach below 30% RH, the comfort of field operators is facilitated (the optimum humidity of a person is 45% RH-65% RH), the production capacity regulation of the workshop in the plum rain season in summer is facilitated, and the energy consumption of a clean area is reduced. In the whole production process, the acid source and the alkali source are not in direct contact, so that the related production materials can be suitable for short-term storage, and the management requirements of a supply chain can be flexibly met. The sensitivity of the produced finished product to humidity is also obviously reduced in the eating process, and the quality and the flavor maintenance of the finished product after the opening can be prolonged.
The invention has wide selection requirements on sugar alcohol and acid source, namely, the invention can reduce the difficulty of developing the formula of the micro-bubble tablet product.
The processing environment requirement is low: according to the technical scheme, the direct contact of an acid source and an alkali source before tabletting can be avoided, so that the hygroscopicity of the total mixed material is reduced, the humidity of a processing environment is not particularly limited, and the conventional humidity of 45-65% can meet the production requirement.
The production process is simple: the production of the tabletting preparation can be started only by separately weighing and respectively mixing the materials according to the formula of the acid source and the alkali source, and the complicated separate granulation and drying of the acid source and the alkali source are not needed, and the water activity in the raw materials is not needed to be controlled intentionally.
Flexible supply chain management: because the acid source and the alkali source are stored separately, moisture absorption of raw materials caused by contact of the acid source and the alkali source can be avoided, related production raw materials are stored in a deliberate short-term mode, the situation that the chemical reaction occurs inside the total mixed materials to cause scrapping of the materials is avoided, meanwhile, the materials are conveniently prepared in advance in production, and the flexibility of the whole supply chain is improved.
The stability of the finished product in the using process is ensured: the micro-bubble piece can be stored for 12-24 months without deterioration under the condition of sealing and water resisting, but the package of the product in the eating process of normal customers can not completely isolate the contact of the micro-bubble piece and the external environment, the common micro-bubble piece is very easy to absorb moisture after being unsealed because an acid source and an alkali source are uniformly mixed together, and the tolerance of the double-layer piece acid source and the alkali source to the humidity is higher only by one contact surface, so that the quality and the experience of the product can be more effectively ensured in the conventional eating process.
Drawings
Fig. 1 is a schematic diagram of a product structure.
Detailed Description
Example 1
An oral micro-bubble buccal tablet comprises an acid source layer 1 and an alkali source layer 2 which are pressed and fixed.
The acid source layer 1 is mainly prepared from 40 parts of isomalt, 10 parts of anhydrous citric acid, 0.1 part of sucralose as an acid source layer, 0.5 part of edible essence as an acid source layer and 1 part of magnesium stearate as an acid source layer.
The alkali source layer 2 is mainly prepared from 40 parts of sorbitol, 10 parts of sodium bicarbonate, 2 parts of ascorbic acid, 0.1 part of sucralose, 0.5 part of edible essence and 1 part of magnesium stearate.
A method for preparing an oral cavity micro-bubble buccal tablet comprises the following steps: comprises the following steps:
1. preparing ingredients.
Acid source layer 1: the acid source layer 1 formulation in this example was prepared.
Alkali source layer 2: the formulation of the alkali source layer 2 in this example was prepared.
2. And (3) mixing materials.
Preparing an acid source total mixed material: accurately weighing 40 parts of isomalt, 10 parts of anhydrous citric acid, 0.1 part of sucralose and 0.5 part of edible essence, sieving by a 40-mesh sieve, putting into a three-dimensional mixer, mixing at a rotating speed of 6rpm for 20min, adding 1 part of magnesium stearate of the acid source layer, and mixing for 5min again to obtain the acid source material.
Preparing an alkali source total mixed material: accurately weighing 40 parts of sorbitol, 10 parts of sodium bicarbonate, 2 parts of ascorbic acid, 0.1 part of sucralose as an alkali source layer and 0.5 part of edible essence as the alkali source layer, sieving by using a 40-mesh sieve, putting into a three-dimensional mixer, mixing at the rotating speed of 6rpm for 20min, adding 1 part of magnesium stearate as the alkali source layer, and mixing again for 5min to obtain the alkali source material.
3. And (5) layering and tabletting.
The acid source material and the alkali source material form a structure for fixing the acid source layer 1 and the alkali source layer 2, (acid source filling, tamping pressure, alkali source filling, secondary prepressing and main pressing).
The devices used in the above process are all existing devices.
Example 2
An oral micro-bubble buccal tablet comprises an acid source layer 1 and an alkali source layer 2 which are pressed and fixed.
The acid source layer 1 is mainly prepared from 70 parts of maltitol, 25 parts of tartaric acid, 0.3 part of stevioside serving as an acid source layer, 2 parts of edible essence serving as the acid source layer and 2 parts of magnesium stearate serving as the acid source layer.
The alkali source layer 2 is mainly prepared from 70 parts of sorbitol, 25 parts of sodium bicarbonate, 5 parts of ascorbic acid, 0.3 part of stevioside serving as an alkali source layer, 2 parts of edible essence serving as the alkali source layer and 2 parts of magnesium stearate serving as the alkali source layer.
A method for preparing an oral cavity micro-bubble buccal tablet comprises the following steps: comprises the following steps:
1. preparing ingredients.
Acid source layer 1: the acid source layer 1 formulation in this example was prepared.
Alkali source layer 2: the formulation of the alkali source layer 2 in this example was prepared.
2. And (3) mixing materials.
Preparing an acid source total mixed material: accurately weighing 70 parts of maltitol, 25 parts of tartaric acid, 0.3 part of stevioside serving as an acid source layer and 2 parts of edible essence serving as the acid source layer, sieving by using a 40-mesh sieve, putting into a three-dimensional mixer, mixing for 40min at the rotating speed of 8rpm, adding 2 parts of magnesium stearate serving as the acid source layer, and mixing for 15min again to obtain the acid source material.
Preparing an alkali source total mixed material: accurately weighing 70 parts of sorbitol, 25 parts of sodium bicarbonate, 5 parts of ascorbic acid, 0.3 part of stevioside in an alkali source layer and 2 parts of edible essence in the alkali source layer, sieving by using a 40-mesh sieve, putting into a three-dimensional mixer, mixing for 40min at the rotating speed of 8rpm, adding 2 parts of magnesium stearate in the alkali source layer, and mixing for 15min again to obtain the alkali source material.
3. And (5) layering and tabletting.
The acid source material and the base source material are compressed together in two layers.
Example 3
An oral micro-bubble buccal tablet comprises an acid source layer 1 and an alkali source layer 2 which are pressed and fixed.
The acid source layer 1 is mainly prepared from 50 parts of isomalt, 15 parts of tartaric acid, 0.2 part of stevioside serving as an acid source layer, 1.5 parts of edible essence serving as the acid source layer and 1.5 parts of magnesium stearate serving as the acid source layer.
The alkali source layer 2 is mainly prepared from 60 parts of sorbitol, 20 parts of sodium bicarbonate, 4 parts of ascorbic acid, 0.2 part of stevioside serving as an alkali source layer, 1.5 parts of edible essence serving as the alkali source layer and 1.5 parts of magnesium stearate serving as the alkali source layer.
1. Preparing ingredients.
Acid source layer 1: the acid source layer 1 formulation in this example was prepared.
Alkali source layer 2: the preparation of the alkali source layer in the present example was carried out according to the formula 2.
2. And (3) mixing materials.
Preparing an acid source total mixed material: accurately weighing 50 parts of isomalt, 15 parts of tartaric acid, 0.2 part of stevioside serving as an acid source layer and 1.5 parts of edible essence serving as the acid source layer, sieving by using a 40-mesh sieve, putting into a three-dimensional mixer, mixing for 30min at a rotating speed of 7rpm, adding 1.5 parts of magnesium stearate serving as the acid source layer, and mixing for 10min again to obtain the acid source material.
Preparing an alkali source total mixed material: accurately weighing 60 parts of sorbitol, 20 parts of sodium bicarbonate, 4 parts of ascorbic acid, 0.2 part of stevioside in an alkali source layer and 1.5 parts of edible essence in the alkali source layer, sieving by using a 40-mesh sieve, putting into a three-dimensional mixer, mixing for 30min at the rotating speed of 7rpm, adding 1.5 parts of magnesium stearate in the alkali source layer, and mixing for 10min again to obtain the alkali source material.
3. And (5) layering and tabletting.
The acid source material and the base source material are compressed together in two layers.
Example 4
An oral micro-bubble buccal tablet comprises an acid source layer 1 and an alkali source layer 2 which are pressed and fixed.
The acid source layer 1 is mainly prepared from 60 parts of maltitol, 18 parts of anhydrous citric acid, 0.15 part of sucralose as an acid source layer, 1 part of edible essence as an acid source layer and 1.3 parts of magnesium stearate as an acid source layer.
The alkali source layer 2 is mainly prepared from 50 parts of sorbitol, 18 parts of sodium bicarbonate, 4 parts of ascorbic acid, 0.25 part of sucralose, 1 part of edible essence and 1.3 parts of magnesium stearate.
A method for preparing an oral cavity micro-bubble buccal tablet comprises the following steps: comprises the following steps:
1. preparing ingredients.
Acid source layer 1: the acid source layer 1 formulation in this example was prepared.
Alkali source layer 2: the materials were prepared according to the acid source layer 2 formulation in this example.
2. And (3) mixing materials.
Preparing an acid source total mixed material: accurately weighing 60 parts of maltitol, 18 parts of anhydrous citric acid, 0.15 part of sucralose as an acid source layer and 1 part of edible essence as the acid source layer, sieving by a 40-mesh sieve, putting into a three-dimensional mixer, mixing for 25min at the rotating speed of 7rpm, adding 1.3 parts of magnesium stearate as the acid source layer, and mixing for 12min again to obtain the acid source material.
Preparing an alkali source total mixed material: accurately weighing 50 parts of sorbitol, 18 parts of sodium bicarbonate, 4 parts of ascorbic acid, 0.25 part of sucralose as an alkali source layer and 1 part of edible essence as the alkali source layer, sieving by using a 40-mesh sieve, putting into a three-dimensional mixer, mixing for 25min at the rotating speed of 7rpm, adding 1.3 parts of magnesium stearate as the alkali source layer, and mixing for 12min again to obtain the alkali source material.
3. And (5) layering and tabletting.
The acid source material and the base source material are compressed together in two layers.
Evaluation of the obtained bilayer tablet:
compressibility: almost no moisture absorption exists in the production process, sticking does not occur even if the tablet is pressed for a long time, and smooth production can be realized.
Appearance: the tablet surface is smooth, the texture is uniform, and the boundary between the acid source and the alkali source is clear.
The mouthfeel is as follows: has the characteristic taste of the product, is sour, sweet and delicious, and has proper bubble feeling.
Physical and chemical treatment: the difference of the tablet weight RSD value is less than 2%, the friability is less than 0.5%, and the hardness is 8-12 kg/cm2。
And (3) normal temperature stability: the edible state (not strictly sealed) is stored for 30 days at room temperature (20-25 ℃, 50-70% RH), and the sense, taste and physicochemical changes are not obvious.
Stability of accelerated test: temporarily storing for 90 days at 40 ℃ and 75% RH, and no obvious changes occur in sense, taste and physicochemical property.
Photograph (same formula but acid source and alkali source are mixed and directly pressed into single layer tablet).
Compressibility: the hygroscopicity is strong in the production process, the humidity of a clean area needs to be controlled (less than 30%), occasionally sticking occurs when the tablet is pressed for a long time, the smooth production can be realized, and the productivity is limited.
Appearance: smooth sheet surface and uniform texture.
The mouthfeel is as follows: has the characteristic taste of the product, is sour, sweet and delicious, and has proper bubble feeling.
Physical and chemical treatment: the difference of the tablet weight RSD value is less than 5%, the friability is less than 0.5%, and the hardness is 8-18 kg/cm2The hardness fluctuation is relatively large.
And (3) normal temperature stability: when the tablets are stored for 10 days in an edible state (not strictly sealed) at room temperature (20-25 ℃ and 50-70% RH), the tablets obviously absorb moisture and are slightly soft, the mouthfeel obviously changes, the bubble feeling is slight, and the surfaces of the tablets become rough.
Stability of accelerated test: temporarily storing for 90 days at 40 ℃ and 75% RH, and no obvious changes occur in sense, taste and physicochemical property.
In conclusion, the same formula is used for tabletting by a single-layer tablet process and a double-layer tablet process, the produced micro-bubble tablets have similar mouthfeel, but the double-layer tablets have lower requirements on production environment, the stability in the production process is higher, and the micro-bubble tablets have obvious moisture absorption resistance in conventional storage.
Claims (10)
1. An oral cavity micro-bubble buccal tablet comprises a fixed acid source layer (1) and an alkali source layer (2), and is characterized in that:
the acid source layer (1) is mainly prepared from 40-70 parts of isomaltitol/maltitol, 10-25 parts of anhydrous citric acid/tartaric acid and 0.1-0.3 part of acid source layer sucralose/acid source layer stevioside;
the alkali source layer (2) is mainly prepared from 40-70 parts of sorbitol, 10-25 parts of sodium bicarbonate, 2-5 parts of ascorbic acid and 0.1-0.3 part of sucralose as an alkali source layer/stevioside as an alkali source layer;
the parts are all parts by mass.
2. The oral microbubble buccal tablet according to claim 1, wherein:
the acid source layer (1) also comprises 0.5-2 parts of edible essence of the acid source layer and 1-2 parts of magnesium stearate of the acid source layer;
the alkali source layer (2) also contains 0.5-2 parts of alkali source layer edible essence and 1-2 parts of alkali source layer magnesium stearate.
3. The oral microbubble buccal tablet according to claim 1, wherein:
the acid source layer (1) is mainly prepared from 40 parts of isomalt, 10 parts of anhydrous citric acid and 0.1 part of sucralose serving as an acid source layer;
the alkali source layer (2) is mainly prepared from 40 parts of sorbitol, 10 parts of sodium bicarbonate, 2 parts of ascorbic acid and 0.1 part of sucralose serving as an alkali source layer.
4. The oral microbubble buccal tablet according to claim 1, wherein:
the acid source layer (1) is mainly prepared from 70 parts of maltitol, 25 parts of tartaric acid and 0.3 part of stevioside serving as the acid source layer;
the alkali source layer (2) is mainly prepared from 70 parts of sorbitol, 25 parts of sodium bicarbonate, 5 parts of ascorbic acid and 0.3 part of stevioside serving as an alkali source layer.
5. The oral microbubble buccal tablet according to claim 1, wherein:
the acid source layer (1) is mainly prepared from 50 parts of isomaltitol, 15 parts of tartaric acid and 0.2 part of stevioside serving as an acid source layer;
the alkali source layer (2) is mainly prepared from 60 parts of sorbitol, 20 parts of sodium bicarbonate, 4 parts of ascorbic acid and 0.2 part of stevioside serving as an alkali source layer.
6. A method for preparing an oral cavity micro-bubble buccal tablet comprises the following steps: the method is characterized by comprising the following steps:
1) preparing ingredients;
an acid source layer: 40-70 parts of isomalt/maltitol, 10-25 parts of anhydrous citric acid/tartaric acid and 0.1-0.3 part of sucralose as an acid source layer/stevioside as an acid source layer;
an alkali source layer: 40-70 parts of sorbitol, 10-25 parts of sodium bicarbonate, 2-5 parts of ascorbic acid and 0.1-0.3 part of sucralose as an alkali source layer/stevioside as an alkali source layer;
2) preparing a mixed material;
uniformly mixing materials of an acid source layer; uniformly mixing the materials of the alkali source layer;
3) and layering and tabletting.
7. The method for preparing an oral microbubble buccal tablet according to claim 6: the method is characterized by comprising the following steps:
the acid source layer (1) is mainly prepared from 40 parts of isomalt, 10 parts of anhydrous citric acid and 0.1 part of sucralose serving as an acid source layer;
the alkali source layer (2) is mainly prepared from 40 parts of sorbitol, 10 parts of sodium bicarbonate, 2 parts of ascorbic acid and 0.1 part of sucralose serving as an alkali source layer.
8. The method for preparing an oral microbubble buccal tablet according to claim 6: the method is characterized by comprising the following steps:
the acid source layer (1) is mainly prepared from 70 parts of maltitol, 25 parts of tartaric acid and 0.3 part of stevioside serving as the acid source layer;
the alkali source layer (2) is mainly prepared from 70 parts of sorbitol, 25 parts of sodium bicarbonate, 5 parts of ascorbic acid and 0.3 part of stevioside serving as an alkali source layer.
9. The method for preparing an oral microbubble buccal tablet according to claim 6: the method is characterized by comprising the following steps:
the acid source layer (1) is mainly prepared from 50 parts of isomaltitol, 15 parts of tartaric acid and 0.2 part of stevioside serving as an acid source layer;
the alkali source layer (2) is mainly prepared from 60 parts of sorbitol, 20 parts of sodium bicarbonate, 4 parts of ascorbic acid and 0.2 part of stevioside serving as an alkali source layer.
10. The method for preparing an oral microbubble buccal tablet according to claim 6: the method is characterized by comprising the following steps:
the acid source layer (1) also comprises 0.5-2 parts of edible essence of the acid source layer and 1-2 parts of magnesium stearate of the acid source layer;
the alkali source layer (2) also contains 0.5-2 parts of alkali source layer edible essence and 1-2 parts of alkali source layer magnesium stearate.
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