CN116570572A - Gastric-soluble film coating premix and preparation method thereof - Google Patents
Gastric-soluble film coating premix and preparation method thereof Download PDFInfo
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- 239000007888 film coating Substances 0.000 title claims abstract description 54
- 238000009501 film coating Methods 0.000 title claims abstract description 54
- 238000002360 preparation method Methods 0.000 title abstract description 20
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 272
- 238000002156 mixing Methods 0.000 claims abstract description 70
- 239000002131 composite material Substances 0.000 claims abstract description 64
- 239000000853 adhesive Substances 0.000 claims abstract description 41
- 230000001070 adhesive effect Effects 0.000 claims abstract description 41
- 239000004014 plasticizer Substances 0.000 claims abstract description 39
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 39
- 239000003086 colorant Substances 0.000 claims abstract description 38
- 239000003605 opacifier Substances 0.000 claims abstract description 29
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 28
- 239000001116 FEMA 4028 Substances 0.000 claims abstract description 28
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims abstract description 28
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims abstract description 28
- 229960004853 betadex Drugs 0.000 claims abstract description 28
- SOQBVABWOPYFQZ-UHFFFAOYSA-N oxygen(2-);titanium(4+) Chemical group [O-2].[O-2].[Ti+4] SOQBVABWOPYFQZ-UHFFFAOYSA-N 0.000 claims abstract description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 25
- 235000019640 taste Nutrition 0.000 claims abstract description 23
- 235000013162 Cocos nucifera Nutrition 0.000 claims abstract description 15
- 244000060011 Cocos nucifera Species 0.000 claims abstract description 15
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 15
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 78
- 239000000203 mixture Substances 0.000 claims description 72
- 239000000843 powder Substances 0.000 claims description 67
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 39
- 238000000227 grinding Methods 0.000 claims description 36
- 238000000498 ball milling Methods 0.000 claims description 33
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical group O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 28
- 239000007788 liquid Substances 0.000 claims description 27
- 238000005336 cracking Methods 0.000 claims description 26
- 239000000796 flavoring agent Substances 0.000 claims description 26
- 235000013355 food flavoring agent Nutrition 0.000 claims description 26
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 24
- 229920001531 copovidone Polymers 0.000 claims description 24
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 24
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 24
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 24
- 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 24
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 24
- 238000001035 drying Methods 0.000 claims description 23
- 229920001046 Nanocellulose Polymers 0.000 claims description 17
- 238000007710 freezing Methods 0.000 claims description 14
- 230000008014 freezing Effects 0.000 claims description 14
- 239000010903 husk Substances 0.000 claims description 13
- 235000013399 edible fruits Nutrition 0.000 claims description 12
- 239000000049 pigment Substances 0.000 claims description 12
- 238000007873 sieving Methods 0.000 claims description 12
- 235000019441 ethanol Nutrition 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000008213 purified water Substances 0.000 claims description 7
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 5
- 229940068886 polyethylene glycol 300 Drugs 0.000 claims description 5
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims description 5
- 239000008176 lyophilized powder Substances 0.000 claims description 3
- 238000010298 pulverizing process Methods 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 239000000454 talc Substances 0.000 claims 1
- 229910052623 talc Inorganic materials 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 17
- 239000003814 drug Substances 0.000 abstract description 10
- 230000007774 longterm Effects 0.000 abstract description 4
- 229920002678 cellulose Polymers 0.000 abstract description 2
- 239000001913 cellulose Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000011248 coating agent Substances 0.000 description 23
- 238000000576 coating method Methods 0.000 description 22
- 239000003826 tablet Substances 0.000 description 13
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical group O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 12
- 238000010438 heat treatment Methods 0.000 description 11
- 230000003301 hydrolyzing effect Effects 0.000 description 10
- 238000010521 absorption reaction Methods 0.000 description 9
- 238000004321 preservation Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 230000004584 weight gain Effects 0.000 description 4
- 235000019786 weight gain Nutrition 0.000 description 4
- 239000011247 coating layer Substances 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000007940 sugar coated tablet Substances 0.000 description 3
- 235000019658 bitter taste Nutrition 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 238000009495 sugar coating Methods 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 230000009477 glass transition Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 235000019633 pungent taste Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000005303 weighing Methods 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P60/00—Technologies relating to agriculture, livestock or agroalimentary industries
- Y02P60/80—Food processing, e.g. use of renewable energies or variable speed drives in handling, conveying or stacking
- Y02P60/87—Re-use of by-products of food processing for fodder production
Abstract
A gastric-soluble film coating premix and a preparation method thereof belong to the technical field of pharmaceutical auxiliary materials, and the premix comprises a composite film forming agent, a light shielding agent, an adhesive, a moisture-proof agent, an anticracking agent, a glidant, a plasticizer, a taste agent and a colorant; beta-cyclodextrin is added into the composite film forming agent; the opacifier is modified titanium dioxide; the adhesive is polyvinylpyrrolidone; the moisture-proof agent is diatomite; the anticracking agent is coconut Pi Najing cellulose, and the film coating premix is prepared by a special mixing method, so that the film is compact and thinner, has strong adhesive force, is not easy to absorb moisture, mildew and crack, can meet the long-term medication requirement of patients, is safe and healthy, and has good practical value.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical excipients, and particularly relates to a gastric-soluble film coating premix and a preparation method thereof.
Background
Along with the continuous innovation and development of the pharmaceutical auxiliary material technology, the medicine coating technology is changed from sugar coating development to film coating, and the film coating has the advantages of good stability, short coating time, less weight gain and good moisture resistance, and gradually replaces sugar coating. The medicine film coating is mainly used for covering the pungent smell, bitter taste and unattractive color so as to improve the medicine taking compliance. In addition, the film coating can also delay the release time of the medicine, and is suitable for the administration and the absorption of different parts; thus, film coatings are classified into gastric-soluble film coatings containing film-forming agents that dissolve in water and gastric juice, and enteric-soluble film coatings containing film-forming agents that are insoluble in gastric juice but soluble in intestinal juice.
In recent years, with the appearance of various novel high molecular polymers and the advent of novel coating equipment, film coating is popularized and developed, film coating agents generally consist of film forming agents, plasticizers, solid additives, auxiliaries and the like, and during production, the materials are mixed uniformly in advance according to a certain formula proportion and a specific production process to form a complete production material, namely film coating premix. In the film coating premix, various auxiliary materials are not simply mixed, and the mechanical properties of the coating agent, including indexes such as tensile strength, young modulus and glass transition temperature of a film, are obviously influenced due to different combination types and proportions of film forming materials, plasticizers and colorants, so that the film coating premix has unique advantages compared with a single film forming polymer material. In order to adapt to different physical and chemical properties of the medicinal components, the formulation and the method of the film coating are different. Especially, the Chinese medicinal component tablet contains various Chinese medicinal powder, has pungent taste and bitter taste, and is usually sugar-coated tablet, but the Chinese medicinal component is generally a long-term administration medicine, the sugar-coated tablet can greatly increase the weight of the tablet, and the polysaccharide component is not friendly to patients who are contraindicated for sugar and diabetics, and affects the health; the traditional Chinese medicine powder is extremely easy to absorb moisture, mildew, crack, not easy to preserve, and has reduced efficacy; however, due to the high content of various powders of the traditional Chinese medicine components, the film coating has the problems of poor adhesive force, which leads to easy moisture absorption and cracking, in particular to the water-based film coating, namely the gastric-soluble film coating, which leads to easy moisture absorption and deterioration of tablets and unstable coating quality if the adhesive force is poor, thereby bringing great hidden danger to the administration of the tablets.
Disclosure of Invention
The sugar-coated tablet is adopted for long-term administration, so that the health is affected, and moisture absorption, mildew and cracking are very easy to occur; the invention provides a gastric-soluble film coating premix and a preparation method thereof, wherein beta-cyclodextrin, modified titanium dioxide, polyvinylpyrrolidone, diatomite, coconut Pi Najing cellulose NCC and the like are added, and a special mixing method is adopted to prepare the film coating premix. The specific technical scheme is as follows:
the gastric-soluble film coating premix comprises, by mass, 30-50 parts of a composite film forming agent, 0.5-2 parts of a light shielding agent, 0.1-2 parts of an adhesive, 0.5-2 parts of a moisture-proof agent, 0.2-2 parts of an anticracking agent, 2-5 parts of a glidant, 8-12 parts of a plasticizer, 0.5-5 parts of a taste agent and 0.5-5 parts of a coloring agent; the composite film forming agent comprises, by mass, 2-6 parts of hydroxypropyl methylcellulose, 1-3 parts of polyvinyl alcohol, 1-2 parts of copovidone and 0.01-0.1 part of beta-cyclodextrin; the opacifier is modified titanium dioxide; the adhesive is polyvinylpyrrolidone; the moisture-proof agent is diatomite; the anticracking agent is nanocrystalline cellulose NCC.
In the technical scheme, the glidant is talcum powder; the plasticizer is polyethylene glycol 6000, polyethylene glycol 300 or polyethylene glycol 400; the flavoring agent is edible fruit flavoring agent; the colorant is edible pigment;
in the technical scheme, the nanocrystalline cellulose NCC is prepared by taking coconut husk as a raw material through hydrolysis.
In the technical scheme, the modified titanium dioxide is blue rutile titanium dioxide obtained by performing high-temperature heat treatment on rutile titanium dioxide for 10-20 hours at 1800-2000 ℃ under the protection of nitrogen.
The preparation method of the gastric-soluble film coating premix comprises the following steps:
s1, pretreatment:
freezing the dampproof agent in liquid nitrogen for 1-2 h, then crushing and grading or grinding the dampproof agent into powder with the median granularity smaller than 2um, and then placing the powder in liquid nitrogen for preservation to obtain dampproof agent freeze-dried powder for later use;
taking a light screening agent, taking absolute ethyl alcohol as a grinding medium, wet ball grinding for 30-50 min, and then drying at 80-100 ℃ to obtain light screening agent ball milling powder for later use;
s2, preparing a composite film forming agent:
uniformly mixing 2-6 parts by mass of hydroxypropyl methylcellulose, 1-3 parts by mass of polyvinyl alcohol, 1-2 parts by mass of copovidone and 0.01-0.1 part by mass of beta-cyclodextrin to obtain a composite film forming agent;
s3, preparing a premix:
taking 0.5-2 parts by mass of moisture-proof agent freeze-dried powder, 1-2 parts by mass of glidant and 0.2-2 parts by mass of anticracking agent, and uniformly mixing the moisture-proof agent and the glidant to obtain a mixture A; then, carrying out air flow mixing on the mixture A and the anti-cracking agent for 30-60 min to obtain a mixture B;
taking 30-50 parts of composite film forming agent, 1-3 parts of glidant, 8-12 parts of plasticizer and 0.5-5 parts of taste agent according to parts by weight, uniformly mixing with 10-25 parts of purified water or ethanol with the volume concentration of 25-40% for 1-2 hours, then drying at 35-45 ℃ and uniformly mixing to obtain a mixture C;
mixing the mixture B, the mixture C, 0.1-2 parts of adhesive, 0.5-5 parts of colorant and 0.5-2 parts of opacifier ball mill powder for 1-2 hours by dry ball milling, sieving with a 80-180 mesh sieve, and taking the undersize to obtain the premix.
Compared with the prior art, the gastric-soluble film coating premix and the preparation method thereof have the beneficial effects that:
1. according to the invention, the modified titanium dioxide is added to the coating premix as the opacifier, so that the blue opacifier has a better shading effect, the dosage of the opacifier can be reduced, and the coating film is thinned; in addition, the light-shading agent is used by being matched with diatomite, so that the light-shading effect is further improved, and the dosage cost of the light-shading agent is saved.
2. The composite film forming agent of the coating premix disclosed by the invention is added with a small amount of beta-cyclodextrin, so that partial cohesiveness can be increased, talcum powder is matched for flow-assisted dispersion, the film forming compactness effect is improved, and meanwhile, the problem of poor compounding property of the composite film forming agent cannot be caused by the beta-cyclodextrin consumption.
3. The polyvinyl pyrrolidone is added into the coating premix and is matched with diatomite for use, so that the coating adhesion strength can be improved; in addition, the diatomite has a dehumidifying effect; the diatomite has smaller particle size, and the coated diatomite cannot be exposed on the surface of the coating, so that moisture in the environment cannot be absorbed, but once the moisture in the environment enters the coating layer or the tablet through the weak part of the coating, the diatomite has a barrier effect, and moisture entering the tablet can be reduced after the diatomite absorbs moisture, so that the traditional Chinese medicine components in the tablet are prevented from mildew.
4. According to the invention, nanocrystalline cellulose NCC is added into the coating premix, the nanocrystalline cellulose NCC is prepared from coconut husk, the toughness and the tensile strength are higher, the cracking of a coating layer is effectively prevented, and particularly after diatomite absorbs moisture, the expansion cracking can be reduced, and more moisture is prevented from entering the tablet through the crack.
5. The coating premix disclosed by the invention has the advantages that various auxiliary materials are less to add, a dense film-forming coating layer with strong adhesive force can be realized, and the consumption cost of the auxiliary materials is saved.
6. According to the preparation method, the diatomite as a moisture-proof agent is designed to be subjected to liquid nitrogen freeze-drying, so that the viscosity is reduced, and the diatomite is convenient to crush into smaller granularity; the diatomite can be kept dry after being stored under the freezing of liquid nitrogen, and good moisture resistance is ensured after the premix is compounded.
7. According to the preparation method, the opacifier modified titanium dioxide is designed for wet ball milling, so that the surface morphology of the titanium dioxide is improved, the edges and corners are reduced, the filling fluidity of the titanium dioxide is better, the dispersion is uniform, and the shading effect is improved.
8. According to the preparation method, the moisture-proof agent freeze-dried powder, the glidant and the anti-cracking agent are mixed firstly, and because the granularity of the anti-cracking agent and the moisture-proof agent is small, the anti-cracking agent and the moisture-proof agent are not well dispersed and mixed in various materials, so that the pre-mixing is performed, wherein the moisture-proof agent has certain viscosity, part of the glidant is added to improve the smooth flow dispersibility, and then the moisture-proof agent is mixed with the anti-cracking agent, so that the dispersion and mixing uniformity of the anti-cracking agent can be improved. If the method is carried out according to the method that all the raw materials are mixed together, the mixing time is increased, and even if the mixing time is increased, a better uniform effect cannot be achieved; if the mixing time is increased, the particle structure of various raw materials can be damaged, and the particles are finely crushed, so that the moisture absorption is not facilitated, the coating strength is low, and the coating is easy to peel and crack.
In conclusion, the premix prepared by the invention has good film forming, strong adhesive force, less possibility of moisture absorption, mildew and cracking, film forming weight gain of less than 3.5%, moisture absorption expansion rate of less than 3.5%, mildew rate of less than 2% and cracking rate of 3%, can meet the long-term medication requirement of patients, and has good practical value.
Detailed Description
The invention will be further illustrated with reference to specific examples, but the invention is not limited to these examples.
Example 1
The gastric-soluble film coating premix comprises, by mass, 40 parts of a composite film forming agent, 1 part of a light shielding agent, 1 part of an adhesive, 1 part of a moisture-proof agent, 1 part of an anticracking agent, 3 parts of a glidant, 10 parts of a plasticizer, 2 parts of a taste agent and 3 parts of a colorant.
Wherein the composite film forming agent comprises, by mass, 4 parts of hydroxypropyl methylcellulose, 2 parts of polyvinyl alcohol, 1 part of copovidone and 0.05 part of beta-cyclodextrin. The opacifier is modified titanium dioxide, and the modified titanium dioxide is blue rutile titanium dioxide obtained by carrying out high-temperature heat treatment on rutile titanium dioxide for 18 hours at 2000 ℃ under the protection of nitrogen. The adhesive is polyvinylpyrrolidone. The moisture-proof agent is diatomite. The anticracking agent is nanocrystalline cellulose NCC, which is prepared by hydrolyzing coconut husk. The glidant is talcum powder. The plasticizer is polyethylene glycol 6000. The flavoring agent is edible fruit flavoring agent. The colorant is edible pigment.
The preparation method of the gastric-soluble film coating premix comprises the following steps:
s1, pretreatment:
freezing the dampproof agent in liquid nitrogen for 2 hours, then crushing and grading or grinding the dampproof agent into powder with the median granularity of 800nm, and then placing the powder in liquid nitrogen for preservation to obtain dampproof agent freeze-dried powder for later use;
taking a light-shading agent, using absolute ethyl alcohol as a grinding medium, performing wet ball grinding for 40min, and then drying at 100 ℃ to obtain light-shading agent ball-milling powder for later use;
s2, preparing a composite film forming agent:
uniformly mixing 4 parts of hydroxypropyl methylcellulose, 2 parts of polyvinyl alcohol, 1 part of copovidone and 0.05 part of beta-cyclodextrin according to parts by weight to obtain a composite film forming agent;
s3, preparing a premix:
taking 1 part of dampproof agent freeze-dried powder, 2 parts of glidant and 1 part of anticracking agent according to parts by weight, and uniformly mixing the dampproof agent and the glidant to obtain a mixture A; then carrying out air flow mixing on the mixture A and the anti-cracking agent for 50min to obtain a mixture B;
according to the parts by weight, 40 parts of composite film forming agent, 1 part of glidant, 10 parts of plasticizer and 2 parts of taste agent are taken, evenly mixed with 15 parts of ethanol with volume concentration of 30% for 1.5 hours, and then dried at 40 ℃ and evenly mixed to obtain a mixture C;
and (3) carrying out dry ball milling mixing on the mixture B, the mixture C, 1 part of the adhesive, 3 parts of the colorant and 1 part of the opacifier ball mill for 1.5 hours, sieving with a 80-mesh sieve, and taking the undersize to obtain the premix.
Example 2
The gastric-soluble film coating premix comprises, by mass, 30 parts of a composite film forming agent, 0.5 part of a light shielding agent, 0.1 part of an adhesive, 0.5 part of a moisture-proof agent, 0.2 part of an anticracking agent, 2 parts of a glidant, 8 parts of a plasticizer, 0.5 part of a taste agent and 0.5 part of a colorant.
Wherein the composite film forming agent comprises 2 parts by mass of hydroxypropyl methylcellulose, 1 part by mass of polyvinyl alcohol, 1 part by mass of copovidone and 0.01 part by mass of beta-cyclodextrin. The opacifier is modified titanium dioxide, and the modified titanium dioxide is blue rutile titanium dioxide obtained by carrying out high-temperature heat treatment on rutile titanium dioxide for 10 hours at 1800 ℃ under the protection of nitrogen. The adhesive is polyvinylpyrrolidone. The moisture-proof agent is diatomite. The anticracking agent is nanocrystalline cellulose NCC, which is prepared by hydrolyzing coconut husk. The glidant is talcum powder. The plasticizer is polyethylene glycol 300. The flavoring agent is edible fruit flavoring agent. The colorant is edible pigment.
The preparation method of the gastric-soluble film coating premix comprises the following steps:
s1, pretreatment:
freezing dampproof agent in liquid nitrogen for 2h, pulverizing, grading or grinding into powder with median granularity of 1um, and storing in liquid nitrogen to obtain dampproof agent lyophilized powder;
taking a light-shading agent, using absolute ethyl alcohol as a grinding medium, performing wet ball grinding for 35min, and then drying at 90 ℃ to obtain light-shading agent ball-milling powder for later use;
s2, preparing a composite film forming agent:
uniformly mixing 2 parts of hydroxypropyl methylcellulose, 1 part of polyvinyl alcohol, 1 part of copovidone and 0.01 part of beta-cyclodextrin according to parts by weight to obtain a composite film forming agent;
s3, preparing a premix:
taking 0.5 part of dampproof agent freeze-dried powder, 1 part of glidant and 0.2 part of anticracking agent according to parts by weight, and uniformly mixing the dampproof agent and the glidant to obtain a mixture A; then carrying out air flow mixing on the mixture A and the anti-cracking agent for 60min to obtain a mixture B;
taking 30 parts of composite film forming agent, 1 part of glidant, 8 parts of plasticizer and 0.5 part of taste agent according to parts by mass, uniformly mixing with 12 parts of ethanol with volume concentration of 25% for 1h, then drying at 35 ℃, and uniformly mixing to obtain a mixture C;
and (3) carrying out dry ball milling and mixing on the mixture B, the mixture C, 0.1 part of the adhesive, 0.5 part of the colorant and 0.5 part of the opacifier ball milling powder for 1h, sieving with a 100-mesh sieve, and taking a screen lower material to obtain the premix.
Example 3
The gastric-soluble film coating premix comprises, by mass, 50 parts of a composite film forming agent, 2 parts of a light shielding agent, 2 parts of an adhesive, 2 parts of a moisture-proof agent, 2 parts of an anticracking agent, 5 parts of a glidant, 12 parts of a plasticizer, 5 parts of a taste agent and 5 parts of a colorant.
Wherein the composite film forming agent comprises 6 parts by mass of hydroxypropyl methylcellulose, 3 parts by mass of polyvinyl alcohol, 2 parts by mass of copovidone and 0.1 part by mass of beta-cyclodextrin. The opacifier is modified titanium dioxide, and the modified titanium dioxide is blue rutile titanium dioxide obtained by carrying out high-temperature heat treatment on rutile titanium dioxide for 20 hours at 2000 ℃ under the protection of nitrogen. The adhesive is polyvinylpyrrolidone. The moisture-proof agent is diatomite. The anticracking agent is nanocrystalline cellulose NCC, which is prepared by hydrolyzing coconut husk. The glidant is talcum powder. The plasticizer is polyethylene glycol 400. The flavoring agent is edible fruit flavoring agent. The colorant is edible pigment.
The preparation method of the gastric-soluble film coating premix comprises the following steps:
s1, pretreatment:
freezing the dampproof agent in liquid nitrogen for 1.5h, then crushing, grading or grinding into powder with the median granularity of 1.5um, and then placing the powder in liquid nitrogen for preservation to obtain dampproof agent freeze-dried powder for later use;
taking a light-shading agent, using absolute ethyl alcohol as a grinding medium, performing wet ball grinding for 50min, and then drying at 100 ℃ to obtain light-shading agent ball-milling powder for later use;
s2, preparing a composite film forming agent:
according to the mass parts, 6 parts of hydroxypropyl methylcellulose, 3 parts of polyvinyl alcohol, 2 parts of copovidone and 0.1 part of beta-cyclodextrin are taken and uniformly mixed to obtain a composite film forming agent;
s3, preparing a premix:
taking 2 parts of dampproof agent freeze-dried powder, 2 parts of glidant and 2 parts of anticracking agent according to parts by weight, and uniformly mixing the dampproof agent and the glidant to obtain a mixture A; then carrying out air flow mixing on the mixture A and the anti-cracking agent for 30min to obtain a mixture B;
taking 50 parts of composite film forming agent, 3 parts of glidant, 12 parts of plasticizer and 5 parts of taste agent according to parts by mass, uniformly mixing with 20 parts of purified water for 2 hours, then drying at 45 ℃, and uniformly mixing to obtain a mixture C;
and (3) carrying out dry ball milling and mixing on the mixture B, the mixture C, 2 parts of the adhesive, 5 parts of the colorant and 2 parts of the opacifier ball milling powder for 1h, sieving with a 110-mesh sieve, and taking a screen lower material to obtain the premix.
Example 4
The gastric-soluble film coating premix comprises, by mass, 30 parts of a composite film forming agent, 2 parts of a light shielding agent, 0.1 part of an adhesive, 2 parts of a moisture-proof agent, 0.2 part of an anticracking agent, 5 parts of a glidant, 8 parts of a plasticizer, 5 parts of a taste agent and 0.5 part of a colorant.
Wherein the composite film forming agent comprises 6 parts by mass of hydroxypropyl methylcellulose, 1 part by mass of polyvinyl alcohol, 2 parts by mass of copovidone and 0.01 part by mass of beta-cyclodextrin. The opacifier is modified titanium dioxide, and the modified titanium dioxide is blue rutile titanium dioxide obtained by carrying out high-temperature heat treatment on rutile titanium dioxide for 10 hours at 2000 ℃ under the protection of nitrogen. The adhesive is polyvinylpyrrolidone. The moisture-proof agent is diatomite. The anticracking agent is nanocrystalline cellulose NCC, which is prepared by hydrolyzing coconut husk. The glidant is talcum powder. The plasticizer is polyethylene glycol 6000. The flavoring agent is edible fruit flavoring agent. The colorant is edible pigment.
The preparation method of the gastric-soluble film coating premix comprises the following steps:
s1, pretreatment:
freezing dampproof agent in liquid nitrogen for 2h, pulverizing, grading or grinding into powder with median particle size of 1.2um, and storing in liquid nitrogen to obtain dampproof agent lyophilized powder;
taking a light-shading agent, using absolute ethyl alcohol as a grinding medium, wet ball grinding for 30min, and then drying at 90 ℃ to obtain light-shading agent ball-milling powder for later use;
s2, preparing a composite film forming agent:
uniformly mixing 6 parts of hydroxypropyl methylcellulose, 1 part of polyvinyl alcohol, 2 parts of copovidone and 0.01 part of beta-cyclodextrin according to parts by weight to obtain a composite film forming agent;
s3, preparing a premix:
taking 2 parts by mass of dampproof agent freeze-dried powder, 2 parts by mass of glidant and 0.2 part by mass of anticracking agent, and uniformly mixing the dampproof agent and the glidant to obtain a mixture A; then carrying out air flow mixing on the mixture A and the anti-cracking agent for 50min to obtain a mixture B;
according to the parts by weight, 30 parts of composite film forming agent, 3 parts of glidant, 8 parts of plasticizer and 5 parts of taste agent are taken, evenly mixed with 20 parts of ethanol with the volume concentration of 40% for 2 hours, and then dried at 35 ℃ and evenly mixed to obtain a mixture C;
and (3) carrying out dry ball milling and mixing on the mixture B, the mixture C, 0.1 part of the adhesive, 0.5 part of the colorant and 2 parts of the opacifier ball milling powder for 2 hours, sieving with a 180-mesh sieve, and taking a screen lower material to obtain the premix.
Example 5
The gastric-soluble film coating premix comprises, by mass, 50 parts of a composite film forming agent, 0.5 part of a light shielding agent, 2 parts of an adhesive, 0.5 part of a moisture-proof agent, 2 parts of an anticracking agent, 2 parts of a glidant, 12 parts of a plasticizer, 0.5 part of a taste agent and 5 parts of a colorant.
Wherein the composite film forming agent comprises 2 parts by mass of hydroxypropyl methylcellulose, 3 parts by mass of polyvinyl alcohol, 1 part by mass of copovidone and 0.1 part by mass of beta-cyclodextrin. The opacifier is modified titanium dioxide, and the modified titanium dioxide is blue rutile titanium dioxide obtained by carrying out high-temperature heat treatment on rutile titanium dioxide for 20 hours at 1800 ℃ under the protection of nitrogen. The adhesive is polyvinylpyrrolidone. The moisture-proof agent is diatomite. The anticracking agent is nanocrystalline cellulose NCC, which is prepared by hydrolyzing coconut husk. The glidant is talcum powder. The plasticizer is polyethylene glycol 300. The flavoring agent is edible fruit flavoring agent. The colorant is edible pigment.
The preparation method of the gastric-soluble film coating premix comprises the following steps:
s1, pretreatment:
freezing the dampproof agent in liquid nitrogen for 1h, then crushing and grading or grinding the dampproof agent into powder with the median granularity of 750nm, and then placing the powder in liquid nitrogen for preservation to obtain dampproof agent freeze-dried powder for later use;
taking a light-shading agent, using absolute ethyl alcohol as a grinding medium, performing wet ball grinding for 30min, and then drying at 80 ℃ to obtain light-shading agent ball-milling powder for later use;
s2, preparing a composite film forming agent:
uniformly mixing 2 parts of hydroxypropyl methylcellulose, 3 parts of polyvinyl alcohol, 1 part of copovidone and 0.1 part of beta-cyclodextrin according to parts by weight to obtain a composite film forming agent;
s3, preparing a premix:
taking 0.5 part of dampproof agent freeze-dried powder, 1 part of glidant and 2 parts of anticracking agent according to parts by weight, and uniformly mixing the dampproof agent and the glidant to obtain a mixture A; then carrying out air flow mixing on the mixture A and the anti-cracking agent for 30min to obtain a mixture B;
taking 50 parts of composite film forming agent, 1 part of glidant, 12 parts of plasticizer and 0.5 part of taste agent according to parts by mass, uniformly mixing with 10 parts of ethanol with the volume concentration of 25% for 1h, then drying at 35 ℃, and uniformly mixing to obtain a mixture C;
and (3) carrying out dry ball milling and mixing on the mixture B, the mixture C, 2 parts of the adhesive, 5 parts of the colorant and 0.5 part of the opacifier ball milling powder for 1h, sieving with a 80-mesh sieve, and taking a screen lower material to obtain the premix.
Example 6
The gastric-soluble film coating premix comprises, by mass, 35 parts of a composite film forming agent, 1.5 parts of a light shielding agent, 0.5 part of an adhesive, 1.2 parts of a moisture-proof agent, 1.5 parts of an anticracking agent, 2.5 parts of a glidant, 8.5 parts of a plasticizer, 2.2 parts of a taste agent and 1.8 parts of a colorant.
Wherein the composite film forming agent comprises 2.5 parts by mass of hydroxypropyl methylcellulose, 1.5 parts by mass of polyvinyl alcohol, 1.2 parts by mass of copovidone and 0.08 part by mass of beta-cyclodextrin. The opacifier is modified titanium dioxide, and the modified titanium dioxide is blue rutile titanium dioxide obtained by carrying out high-temperature heat treatment on rutile titanium dioxide for 13 hours at 18500 ℃ under the protection of nitrogen. The adhesive is polyvinylpyrrolidone. The moisture-proof agent is diatomite. The anticracking agent is nanocrystalline cellulose NCC, which is prepared by hydrolyzing coconut husk. The glidant is talcum powder. The plasticizer is polyethylene glycol 400. The flavoring agent is edible fruit flavoring agent. The colorant is edible pigment.
The preparation method of the gastric-soluble film coating premix comprises the following steps:
s1, pretreatment:
freezing the dampproof agent in liquid nitrogen for 2 hours, then crushing and grading or grinding the dampproof agent into powder with the median granularity of 900nm, and then placing the powder in liquid nitrogen for preservation to obtain dampproof agent freeze-dried powder for later use;
taking a light-shading agent, using absolute ethyl alcohol as a grinding medium, performing wet ball grinding for 40min, and then drying at 95 ℃ to obtain light-shading agent ball-milling powder for later use;
s2, preparing a composite film forming agent:
uniformly mixing 2.5 parts of hydroxypropyl methylcellulose, 1.5 parts of polyvinyl alcohol, 1.2 parts of copovidone and 0.01-0.1 part of beta-cyclodextrin according to parts by weight to obtain a composite film forming agent;
s3, preparing a premix:
taking 1.2 parts of dampproof agent freeze-dried powder, 1 part of glidant and 1.5 parts of anticracking agent according to parts by weight, and uniformly mixing the dampproof agent and the glidant to obtain a mixture A; then carrying out air flow mixing on the mixture A and the anti-cracking agent for 45min to obtain a mixture B;
according to the mass parts, taking 35 parts of composite film forming agent, 1.5 parts of glidant, 8.5 parts of plasticizer and 2.2 parts of taste agent, uniformly mixing with 20 volume concentration 40% ethanol for 2 hours, then drying at 45 ℃ and uniformly mixing to obtain a mixture C;
and (3) carrying out dry ball milling and mixing on the mixture B, the mixture C, 0.5 part of the adhesive, 1.8 parts of the colorant and 1.5 parts of the opacifier ball milling powder for 2 hours, sieving with a 100-mesh sieve, and taking a screen lower material to obtain the premix.
Example 7
The gastric-soluble film coating premix comprises, by mass, 45 parts of a composite film forming agent, 1.6 parts of a light shielding agent, 1.4 parts of an adhesive, 1.8 parts of a moisture-proof agent, 1.2 parts of an anticracking agent, 3.6 parts of a glidant, 11 parts of a plasticizer, 4.5 parts of a taste agent and 4.2 parts of a colorant.
Wherein the composite film forming agent comprises, by mass, 4.5 parts of hydroxypropyl methylcellulose, 2.2 parts of polyvinyl alcohol, 1.6 parts of copovidone and 0.06 part of beta-cyclodextrin. The opacifier is modified titanium dioxide, and the modified titanium dioxide is blue rutile titanium dioxide obtained by performing high-temperature heat treatment on rutile titanium dioxide at 1950 ℃ for 16 hours under the protection of nitrogen. The adhesive is polyvinylpyrrolidone. The moisture-proof agent is diatomite. The anticracking agent is nanocrystalline cellulose NCC, which is prepared by hydrolyzing coconut husk. The glidant is talcum powder. The plasticizer is polyethylene glycol 6000. The flavoring agent is edible fruit flavoring agent. The colorant is edible pigment.
The preparation method of the gastric-soluble film coating premix comprises the following steps:
s1, pretreatment:
freezing the dampproof agent in liquid nitrogen for 1h, then crushing and grading or grinding the dampproof agent into powder with the median granularity of 1um, and then placing the powder in liquid nitrogen for preservation to obtain dampproof agent freeze-dried powder for later use;
taking a light-shading agent, using absolute ethyl alcohol as a grinding medium, performing wet ball grinding for 50min, and then drying at 100 ℃ to obtain light-shading agent ball-milling powder for later use;
s2, preparing a composite film forming agent:
uniformly mixing 4.5 parts by mass of hydroxypropyl methylcellulose, 2.2 parts by mass of polyvinyl alcohol, 1.6 parts by mass of copovidone and 0.06 part by mass of beta-cyclodextrin to obtain a composite film forming agent;
s3, preparing a premix:
taking 1.8 parts of dampproof agent freeze-dried powder, 1 part of glidant and 1.2 parts of anticracking agent according to parts by weight, and uniformly mixing the dampproof agent and the glidant to obtain a mixture A; then carrying out air flow mixing on the mixture A and the anti-cracking agent for 35min to obtain a mixture B;
according to the mass portion, 45 portions of composite film forming agent, 2.6 portions of glidant, 11 portions of plasticizer and 4.5 portions of flavoring agent are taken and evenly mixed with 15 portions of purified water for 2 hours, and then dried at 40 ℃ and evenly mixed to obtain a mixture C;
and (3) carrying out dry ball milling and mixing on the mixture B, the mixture C, 1.4 parts of the adhesive, 4.2 parts of the colorant and 1.6 parts of the opacifier ball milling powder for 2 hours, sieving with a 100-mesh sieve, and taking a screen lower material to obtain the premix.
Example 8
The gastric-soluble film coating premix comprises 48 parts of composite film forming agent, 2 parts of opacifying agent, 0.8 part of adhesive, 1.4 parts of dampproof agent, 0.5 part of anticracking agent, 2.6 parts of glidant, 10.5 parts of plasticizer, 0.5 part of taste agent and 3.5 parts of colorant.
Wherein the composite film forming agent comprises, by mass, 4 parts of hydroxypropyl methylcellulose, 3 parts of polyvinyl alcohol, 1 part of copovidone and 0.1 part of beta-cyclodextrin. The opacifier is modified titanium dioxide, and the modified titanium dioxide is blue rutile titanium dioxide obtained by carrying out high-temperature heat treatment on rutile titanium dioxide for 15 hours at 2000 ℃ under the protection of nitrogen. The adhesive is polyvinylpyrrolidone. The moisture-proof agent is diatomite. The anticracking agent is nanocrystalline cellulose NCC, which is prepared by hydrolyzing coconut husk. The glidant is talcum powder. The plasticizer is polyethylene glycol 6000. The flavoring agent is edible fruit flavoring agent. The colorant is edible pigment.
The preparation method of the gastric-soluble film coating premix comprises the following steps:
s1, pretreatment:
freezing the dampproof agent in liquid nitrogen for 1.5h, then crushing, grading or grinding into powder with the median granularity of 1.6um, and then placing the powder in liquid nitrogen for preservation to obtain dampproof agent freeze-dried powder for later use;
taking a light-shading agent, using absolute ethyl alcohol as a grinding medium, performing wet ball grinding for 30min, and then drying at 80 ℃ to obtain light-shading agent ball-milling powder for later use;
s2, preparing a composite film forming agent:
uniformly mixing 4 parts of hydroxypropyl methylcellulose, 3 parts of polyvinyl alcohol, 1 part of copovidone and 0.1 part of beta-cyclodextrin according to parts by weight to obtain a composite film forming agent;
s3, preparing a premix:
taking 1.4 parts of dampproof agent freeze-dried powder, 1.2 parts of glidant and 0.5 part of anticracking agent according to parts by weight, and uniformly mixing the dampproof agent and the glidant to obtain a mixture A; then carrying out air flow mixing on the mixture A and the anti-cracking agent for 60min to obtain a mixture B;
taking 48 parts of composite film forming agent, 1.4 parts of glidant, 10.5 parts of plasticizer and 0.5 part of taste agent according to parts by mass, uniformly mixing with 18 parts of purified water for 1.5 hours, then drying at 45 ℃ and uniformly mixing to obtain a mixture C;
and (3) carrying out dry ball milling and mixing on the mixture B, the mixture C, 0.8 part of the adhesive, 3.5 parts of the colorant and 2 parts of the opacifier ball milling powder for 2 hours, sieving with a 180-mesh sieve, and taking a screen lower material to obtain the premix.
Example 9
The gastric-soluble film coating premix comprises, by mass, 32 parts of a composite film forming agent, 1.4 parts of a light shielding agent, 1.6 parts of an adhesive, 0.8 part of a moisture-proof agent, 1.6 parts of an anticracking agent, 3 parts of a glidant, 8 parts of a plasticizer, 1 part of a taste agent and 1 part of a colorant.
The composite film forming agent comprises, by mass, 5.5 parts of hydroxypropyl methylcellulose, 1.5 parts of polyvinyl alcohol, 2 parts of copovidone and 0.09 part of beta-cyclodextrin. The opacifier is modified titanium dioxide, and the modified titanium dioxide is blue rutile titanium dioxide obtained by carrying out high-temperature heat treatment on rutile titanium dioxide at 1830 ℃ for 16 hours under the protection of nitrogen. The adhesive is polyvinylpyrrolidone. The moisture-proof agent is diatomite. The anticracking agent is nanocrystalline cellulose NCC, which is prepared by hydrolyzing coconut husk. The glidant is talcum powder. The plasticizer is polyethylene glycol 400. The flavoring agent is edible fruit flavoring agent. The colorant is edible pigment.
The preparation method of the gastric-soluble film coating premix comprises the following steps:
s1, pretreatment:
freezing the dampproof agent in liquid nitrogen for 1h, then crushing and grading or grinding the dampproof agent into powder with the median granularity of 850nm, and then placing the powder in liquid nitrogen for preservation to obtain dampproof agent freeze-dried powder for later use;
taking a light-shading agent, using absolute ethyl alcohol as a grinding medium, performing wet ball grinding for 35min, and then drying at 85 ℃ to obtain light-shading agent ball-milling powder for later use;
s2, preparing a composite film forming agent:
uniformly mixing 5.5 parts by mass of hydroxypropyl methylcellulose, 1.5 parts by mass of polyvinyl alcohol, 2 parts by mass of copovidone and 0.09 part by mass of beta-cyclodextrin to obtain a composite film forming agent;
s3, preparing a premix:
taking 0.8 part of dampproof agent freeze-dried powder, 1.5 parts of glidant and 1.6 parts of anticracking agent according to parts by weight, and uniformly mixing the dampproof agent and the glidant to obtain a mixture A; then carrying out air flow mixing on the mixture A and the anti-cracking agent for 45min to obtain a mixture B;
taking 32 parts of composite film forming agent, 1.5 parts of glidant, 8 parts of plasticizer and 1 part of taste agent according to parts by mass, uniformly mixing with 16 parts of ethanol with the volume concentration of 40% for 1h, then drying at 45 ℃, and uniformly mixing to obtain a mixture C;
and (3) carrying out dry ball milling mixing on 1.6 parts of the mixture B, 1.6 parts of the mixture C, 1 part of the colorant and 1.4 parts of the opacifier ball mill for 1.5 hours, sieving with a 80-mesh sieve, and taking a screen lower material to obtain the premix.
Example 10
The gastric-soluble film coating premix comprises 46 parts by mass of a composite film forming agent, 1.8 parts by mass of a light shielding agent, 0.9 part by mass of an adhesive, 1.4 parts by mass of a moisture-proof agent, 1.6 parts by mass of an anticracking agent, 2.5 parts by mass of a glidant, 8.8 parts by mass of a plasticizer, 4.5 parts by mass of a taste agent and 5 parts by mass of a coloring agent.
The composite film forming agent comprises 6 parts by mass of hydroxypropyl methylcellulose, 2.8 parts by mass of polyvinyl alcohol, 1.6 parts by mass of copovidone and 0.1 part by mass of beta-cyclodextrin. The opacifier is modified titanium dioxide, and the modified titanium dioxide is blue rutile titanium dioxide obtained by carrying out high-temperature heat treatment on rutile titanium dioxide for 17 hours at 1900 ℃ under the protection of nitrogen. The adhesive is polyvinylpyrrolidone. The moisture-proof agent is diatomite. The anticracking agent is nanocrystalline cellulose NCC, which is prepared by hydrolyzing coconut husk. The glidant is talcum powder. The plasticizer is polyethylene glycol 300. The flavoring agent is edible fruit flavoring agent. The colorant is edible pigment.
The preparation method of the gastric-soluble film coating premix comprises the following steps:
s1, pretreatment:
freezing the dampproof agent in liquid nitrogen for 2 hours, then crushing and grading or grinding the dampproof agent into powder with the median granularity of 950nm, and then placing the powder in liquid nitrogen for preservation to obtain dampproof agent freeze-dried powder for later use;
taking a light-shading agent, using absolute ethyl alcohol as a grinding medium, performing wet ball grinding for 40min, and then drying at 100 ℃ to obtain light-shading agent ball-milling powder for later use;
s2, preparing a composite film forming agent:
uniformly mixing 6 parts by mass of hydroxypropyl methylcellulose, 2.8 parts by mass of polyvinyl alcohol, 1.6 parts by mass of copovidone and 0.1 part by mass of beta-cyclodextrin to obtain a composite film forming agent;
s3, preparing a premix:
taking 1.4 parts of dampproof agent freeze-dried powder, 1.2 parts of glidant and 1.6 parts of anticracking agent according to parts by weight, and uniformly mixing the dampproof agent and the glidant to obtain a mixture A; then carrying out air flow mixing on the mixture A and the anti-cracking agent for 55min to obtain a mixture B;
according to the mass portion, 46 portions of composite film forming agent, 2.5 portions of glidant, 8.8 portions of plasticizer and 4.5 portions of taste agent are taken and evenly mixed with 22 portions of purified water for 2 hours, and then dried at 35 ℃ and evenly mixed to obtain a mixture C;
and (3) carrying out dry ball milling and mixing on the mixture B, the mixture C, 0.9 part of the adhesive, 5 parts of the colorant and 1.8 parts of the opacifier ball milling powder for 1h, sieving with a 100-mesh sieve, and taking a sieve-undersize product to obtain the premix.
Coating experiments are carried out on the gastric-soluble film coating premix prepared in the examples 1-10, the coated tablet object is a Chinese medicinal component tablet,
respectively dissolving the gastric-soluble film coating premix of examples 1-10 in purified water, spraying the solution with the mass concentration of 15% into a coating machine, respectively coating 200 tablets with the spraying speed of 100mL/min, the air inlet temperature of 80 ℃ and the air outlet temperature of 45 ℃, and drying to obtain coated tablets for detection:
1. weighing the weights before and after coating respectively, and calculating the weight gain rate;
2. the coated tablets were placed under conditions of 60% humidity and 28 ℃ and the swelling, cracking and mildew conditions were observed and recorded for 3 months.
The results are shown in the following table:
the detection results can show that the weight gain after coating is below 3.5%, namely, under the condition of thinner coating, the coating has good adhesiveness, good effects of resisting moisture absorption expansion, cracking and mildew, the moisture absorption expansion rate is not more than 3%, the cracking breakage rate is not more than 2.5%, and the mildew rate is not more than 1.5%.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.
Claims (10)
1. The gastric-soluble film coating premix is characterized by comprising, by mass, 30-50 parts of a composite film forming agent, 0.5-2 parts of a light shielding agent, 0.1-2 parts of an adhesive, 0.5-2 parts of a moisture-proof agent, 0.2-2 parts of an anticracking agent, 2-5 parts of a glidant, 8-12 parts of a plasticizer, 0.5-5 parts of a flavoring agent and 0.5-5 parts of a coloring agent;
wherein the composite film forming agent comprises, by mass, 2-6 parts of hydroxypropyl methylcellulose, 1-3 parts of polyvinyl alcohol, 1-2 parts of copovidone and 0.01-0.1 part of beta-cyclodextrin; the opacifier is modified titanium dioxide; the adhesive is polyvinylpyrrolidone; the moisture-proof agent is diatomite; the anticracking agent is nanocrystalline cellulose NCC.
2. The gastric-soluble film coating premix of claim 1 wherein the glidant is talc; the plasticizer is polyethylene glycol 6000, polyethylene glycol 300 or polyethylene glycol 400; the flavoring agent is edible fruit flavoring agent; the colorant is edible pigment.
3. The gastric-soluble film-coated premix of claim 1 wherein the nanocrystalline cellulose NCC is nanocrystalline cellulose prepared by hydrolysis of coconut husk.
4. The gastric-soluble film coating premix of claim 1, wherein the modified titanium dioxide is rutile titanium dioxide which is treated for 10-20 hours at 1800-2000 ℃ under the protection of nitrogen, and the blue rutile titanium dioxide is obtained.
5. The method for preparing the gastric-soluble film coating premix of claim 1, comprising the steps of:
s1, pretreatment:
freezing the dampproof agent with liquid nitrogen, pulverizing, grading or grinding into powder with median particle size smaller than 2um, and storing in liquid nitrogen to obtain dampproof agent lyophilized powder;
taking a light-shading agent, using absolute ethyl alcohol as a grinding medium, performing wet ball grinding for 30-50 min, and then drying to obtain light-shading agent ball milling powder for later use;
s2, preparing a composite film forming agent:
uniformly mixing 2-6 parts by mass of hydroxypropyl methylcellulose, 1-3 parts by mass of polyvinyl alcohol, 1-2 parts by mass of copovidone and 0.01-0.1 part by mass of beta-cyclodextrin to obtain a composite film forming agent;
s3, preparing a premix:
taking 0.5-2 parts by mass of moisture-proof agent freeze-dried powder, 1-2 parts by mass of glidant and 0.2-2 parts by mass of anticracking agent, and uniformly mixing the moisture-proof agent and the glidant to obtain a mixture A; then, carrying out air flow mixing on the mixture A and the anti-cracking agent for 30-60 min to obtain a mixture B;
taking 30-50 parts of composite film forming agent, 1-3 parts of glidant, 8-12 parts of plasticizer and 0.5-5 parts of taste agent according to parts by weight, uniformly mixing with 10-25 parts of purified water or ethanol for 1-2 hours, drying and uniformly mixing to obtain a mixture C;
and (3) carrying out dry ball milling mixing on 0.1-2 parts of the mixture B, 0.5-5 parts of the colorant, 0.5-2 parts of the opacifier ball mill for 1-2 hours, sieving, and taking the undersize to obtain the premix.
6. The method for preparing a gastric-soluble film coating premix of claim 5 wherein in S1, the liquid nitrogen freezing time is 1-2 hours.
7. The method of claim 5, wherein in S1, the temperature of the drying is 80-100 ℃.
8. The method for preparing a gastric-soluble film coating premix of claim 5 wherein the concentration of ethanol in S3 is 25-40% by volume.
9. The method of claim 5, wherein in S3, the drying temperature is 35-45 ℃.
10. The method of claim 5, wherein in S3, the number of the sieves is 80 to 180 mesh.
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| US20220218616A1 (en) * | 2019-04-15 | 2022-07-14 | Sunsho Pharmaceutical Co., Ltd. | Tablet and method for producing tablet |
| KR20220105944A (en) * | 2021-01-21 | 2022-07-28 | 주식회사 코피텍 | Composition for Film-Coating Comprising Bentonite |
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