CN109432027B - Preparation process of amoxicillin dispersible tablets - Google Patents
Preparation process of amoxicillin dispersible tablets Download PDFInfo
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- CN109432027B CN109432027B CN201910038624.5A CN201910038624A CN109432027B CN 109432027 B CN109432027 B CN 109432027B CN 201910038624 A CN201910038624 A CN 201910038624A CN 109432027 B CN109432027 B CN 109432027B
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- amoxicillin
- mixture
- dispersible tablets
- disintegrating agent
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- 229960003022 amoxicillin Drugs 0.000 title claims abstract description 66
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 title claims abstract description 66
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 title claims abstract description 66
- 239000007919 dispersible tablet Substances 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 239000000463 material Substances 0.000 claims abstract description 53
- 239000000203 mixture Substances 0.000 claims abstract description 45
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 24
- 239000000314 lubricant Substances 0.000 claims abstract description 23
- 239000007884 disintegrant Substances 0.000 claims abstract description 19
- 229940079593 drug Drugs 0.000 claims abstract description 19
- 238000001035 drying Methods 0.000 claims abstract description 17
- 239000000945 filler Substances 0.000 claims abstract description 16
- 238000002156 mixing Methods 0.000 claims abstract description 15
- 238000000498 ball milling Methods 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 239000012778 molding material Substances 0.000 claims abstract description 6
- 238000012216 screening Methods 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 239000011230 binding agent Substances 0.000 claims abstract description 5
- 239000002245 particle Substances 0.000 claims description 28
- 229920002472 Starch Polymers 0.000 claims description 17
- 239000008107 starch Substances 0.000 claims description 17
- 235000019698 starch Nutrition 0.000 claims description 17
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 13
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 13
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 12
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 12
- 239000000853 adhesive Substances 0.000 claims description 12
- 230000001070 adhesive effect Effects 0.000 claims description 12
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 claims description 12
- 239000004927 clay Substances 0.000 claims description 12
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 12
- 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 description 11
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 11
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 11
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 11
- 239000008101 lactose Substances 0.000 claims description 11
- 239000000600 sorbitol Substances 0.000 claims description 11
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 10
- 229920001353 Dextrin Polymers 0.000 claims description 10
- 239000004375 Dextrin Substances 0.000 claims description 10
- 239000011575 calcium Substances 0.000 claims description 10
- 229910052791 calcium Inorganic materials 0.000 claims description 10
- 235000019425 dextrin Nutrition 0.000 claims description 10
- 239000006188 syrup Substances 0.000 claims description 10
- 235000020357 syrup Nutrition 0.000 claims description 10
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000000741 silica gel Substances 0.000 claims description 5
- 229910002027 silica gel Inorganic materials 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 238000001291 vacuum drying Methods 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims 1
- 238000010298 pulverizing process Methods 0.000 claims 1
- 239000004557 technical material Substances 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 4
- 238000004090 dissolution Methods 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 25
- 238000000034 method Methods 0.000 description 9
- 239000000843 powder Substances 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 238000005336 cracking Methods 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000005550 wet granulation Methods 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 208000030961 allergic reaction Diseases 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction 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
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
-
- 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
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a preparation process of amoxicillin dispersible tablets, which comprises the following steps: step 1, respectively crushing an amoxicillin raw material and auxiliary materials; step 2, placing the crushed amoxicillin raw drug and auxiliary materials into a ball mill for ball milling and mixing to prepare a mixture; step 3, adding ethanol into the mixture prepared in the step 2, uniformly stirring, tabletting, drying, crushing and screening to obtain a primary molding material; step 4, mixing the dried material, the secondary disintegrating agent and the lubricating agent; and 5, tabletting. The auxiliary materials comprise: primary disintegrants, fillers and binders. The amoxicillin dispersible tablets produced by the preparation process provided by the invention are beneficial to ensuring the stability and tabletting forming efficiency of the dispersible tablets, and the dispersible tablets have short disintegration time and good dissolution uniformity, so that the medicine has quick effect and absorption and can increase the bioavailability.
Description
Technical Field
The invention relates to the technical field of medicine synthesis, in particular to a preparation process of amoxicillin dispersible tablets.
Background
The amoxicillin dispersible tablet is a novel tablet prepared by taking amoxicillin as a raw material drug, can be rapidly disintegrated and form uniform suspension when meeting water, thereby solving the problem of poor solubility of amoxicillin in water, being beneficial to rapid tissue absorption, and having the characteristics of high gastrointestinal absorption rate, low side reaction and the like. Most of amoxicillin dispersible tablets in the current market adopt the traditional production process, firstly adopt a proper adhesive to carry out wet granulation, and the granules are dried and then compressed into tablets. The amoxicillin raw material is very sensitive to damp and heat, the traditional wet granulation production process has influence on the product quality, the content is obviously reduced, related substances, particularly high-molecular impurities are obviously increased, and the product stability is poor. In the prior art, amoxicillin is polymerized to form a mixture with different polymerization degrees, which is the main reason for the allergic reaction. The method controls the content of high molecular impurities in the amoxicillin preparation, and is a fundamental way for reducing the allergic reaction of penicillin antibiotics and improving the safety of medicaments.
The amoxicillin dispersible tablets are prepared by a powder direct tabletting method which is commonly adopted at present, the mixture of the medicine and the auxiliary materials is directly tabletted without a granulation process, and the granulation process is avoided, so the amoxicillin dispersible tablets have the outstanding advantages of time saving, energy saving, simple and convenient process, less working procedures, suitability for medicines with unstable damp heat and the like, but have the defects of poor powder fluidity, large tablet weight difference, easy cracking of powder tabletting and the like, so the types and the dosage of active ingredients and the auxiliary materials are very selected, and the crystal forms of the raw materials and the auxiliary materials are good, such as tablets and needles.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: the invention provides a preparation process of amoxicillin dispersible tablets, which solves the problems that the existing direct powder tabletting method for preparing amoxicillin dispersible tablets has the defects of poor powder flowability, large tablet weight difference, easy cracking of powder tablets and the like, and the requirements on raw materials are more critical.
The invention is realized by the following technical scheme:
a preparation process of amoxicillin dispersible tablets comprises the following steps:
step 1, respectively crushing an amoxicillin raw material and auxiliary materials;
step 2, placing the crushed amoxicillin raw drug and auxiliary materials into a ball mill for ball milling and mixing to prepare a mixture;
step 3, adding ethanol into the mixture prepared in the step 2, uniformly stirring, and then sequentially tabletting, drying, crushing and screening to obtain a primary molding material;
step 4, mixing the screened material, the secondary disintegrating agent and the lubricant;
step 5, mixing the dried material, the secondary disintegrating agent and the lubricating agent;
step 6, tabletting;
the auxiliary materials comprise: primary disintegrants, fillers and binders.
Further, in the step 1, the amoxicillin crushed particle size is 40-60 meshes, and the auxiliary materials crushed particle size is 60-80 meshes; in the step 2, the particle size of the mixture after ball milling is 80-100 meshes.
Further, in the step 3, the ratio of the total mass of the mixture to the mass of the added ethanol is 5-7.
Furthermore, the pressure of the tabletting operation is 1.8-2.5 MPa, and the particle size of the sieved material is 40-60 meshes.
Further, in the step 3, vacuum drying is adopted, the drying temperature is 35-50 ℃, and the drying time is 5-10 hours.
Further, in the step 4, the crushed secondary disintegrating agent and the crushed lubricant with the particle size of 60-80 meshes are uniformly mixed with the sieved materials.
Further, the primary disintegrating agent adopts a mixture of sorbitol, dry starch, natural clay magnesium aluminum silicate and croscarmellose sodium; the secondary disintegrating agent adopts sodium carboxymethyl starch.
Furthermore, in the primary disintegrating agent, the mass ratio of the cross-linked sodium carboxymethylcellulose, the dry starch, the natural clay magnesium aluminum silicate and the sorbitol is 1:4:0.5:0.2 in sequence, and the ratio of the dosage of the primary disintegrating agent to the dosage of the secondary disintegrating agent is 1: 0.6.
Further, the filler is a mixture of lactose and calcium hydrophosphate, and the mass ratio of the lactose to the calcium hydrophosphate is 3:1 in sequence; the adhesive is a mixture of syrup, dextrin and high-substituted hydroxypropyl cellulose, and the mass ratio of the syrup, the dextrin and the high-substituted hydroxypropyl cellulose is 1:0.2:0.7 in sequence; the lubricant is silica gel micropowder.
Further, the ratio of the mass of the amoxicillin raw material to the total mass of the auxiliary material, the secondary disintegrant and the lubricant is 3.5-5.0.
The invention has the following advantages and beneficial effects:
according to the invention, through improving the process and optimizing the formula, the problem of the wet-heat stability of the amoxicillin dispersible tablets produced by wet granulation is avoided, and meanwhile, the defects of poor powder flowability, large tablet weight difference, easiness in causing tablet cracking and the like of finished products in the direct powder tabletting process are effectively overcome; the amoxicillin dispersible tablets produced by the preparation process provided by the invention are beneficial to ensuring the stability and tabletting forming efficiency of the dispersible tablets, and the dispersible tablets have short disintegration time and good dissolution uniformity, so that the medicine has quick effect and absorption and can increase the bioavailability.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to examples, and the exemplary embodiments and descriptions thereof are only used for explaining the present invention and are not used as limitations of the present invention.
Example 1
The embodiment provides a preparation process of an amoxicillin dispersible tablet, which comprises the following specific steps:
step 1, respectively crushing an amoxicillin raw drug and auxiliary materials, wherein the crushed particle size of the amoxicillin is 40-60 meshes, and the crushed particle size of the auxiliary materials is 60-80 meshes;
step 2, placing the crushed amoxicillin raw drug and auxiliary materials into a ball mill for ball milling and mixing to prepare a mixture, wherein the particle size of the ball milled mixture is 80-100 meshes;
step 3, adding ethanol into the mixture prepared in the step 2, wherein the ratio of the total mass of the mixture to the mass of the added ethanol is 5; uniformly stirring, tabletting, drying, crushing and screening to obtain a primary molding material, wherein the pressure of tabletting operation is 1.8MPa, and the particle size of the screened material is 40-60 meshes; when the materials are dried, vacuum drying is adopted, the drying temperature is 35 ℃, and the drying time is 10 hours;
step 4, uniformly mixing the crushed secondary disintegrating agent and the lubricant with the particle size of 60-80 meshes with the dried material;
step 5, tabletting;
the mass of the amoxicillin raw drug and the total mass and the mixture ratio of the auxiliary materials, the secondary disintegrating agent and the lubricant are 3.5, specifically, the amoxicillin raw drug is as follows: disintegrant (sum of mass of primary and secondary disintegrants): filling agent: adhesive: the lubricant was 1:0.15:0.09:0.04: 0.01. The auxiliary materials comprise: the primary disintegrating agent, the filling agent and the adhesive are sequentially mixed. The specific formula is as follows:
the primary disintegrating agent is a mixture of sorbitol, dry starch, natural clay magnesium aluminum silicate and croscarmellose sodium; in the primary disintegrating agent, the mass ratio of the croscarmellose sodium to the dry starch to the natural clay magnesium aluminum silicate to the sorbitol is 1:4:0.5:0.2 in sequence; the secondary disintegrating agent adopts sodium carboxymethyl starch; the ratio of the dosage of the primary disintegrating agent to the dosage of the secondary disintegrating agent is 1: 0.6.
The filler is a mixture of lactose and calcium hydrophosphate, and the mass ratio of the lactose to the calcium hydrophosphate is 3:1 in sequence;
the adhesive is a mixture of syrup, dextrin and high-substituted hydroxypropyl cellulose, and the mass ratio of the syrup, the dextrin and the high-substituted hydroxypropyl cellulose is 1:0.2:0.7 in sequence;
the lubricant is silica gel micropowder.
Example 2
The embodiment provides a preparation process of an amoxicillin dispersible tablet, which comprises the following specific steps:
step 1, respectively crushing an amoxicillin raw drug and auxiliary materials, wherein the crushed particle size of the amoxicillin is 40-60 meshes, and the crushed particle size of the auxiliary materials is 60-80 meshes;
step 2, placing the crushed amoxicillin raw drug and auxiliary materials into a ball mill for ball milling and mixing to prepare a mixture, wherein the particle size of the ball milled mixture is 80-100 meshes;
step 3, adding ethanol into the mixture prepared in the step 2, wherein the ratio of the total mass of the mixture to the mass of the added ethanol is 7; uniformly stirring, tabletting, drying, crushing and screening to obtain a primary molding material, wherein the pressure of tabletting operation is 2.1MPa, and the particle size of the screened material is 40-60 meshes; when the materials are dried, vacuum drying is adopted, the drying temperature is 42 ℃, and the drying time is 7 hours;
step 4, uniformly mixing the crushed secondary disintegrating agent and the lubricant with the particle size of 60-80 meshes with the dried material;
step 5, tabletting;
the mass of the amoxicillin raw drug and the total mass and the mixture ratio of the auxiliary materials, the secondary disintegrating agent and the lubricant are 4.2, specifically, the amoxicillin raw drug is as follows: disintegrant (sum of mass of primary and secondary disintegrants): filling agent: adhesive: the lubricant is 1:0.12:0.08:0.03: 0.01. The auxiliary materials comprise: primary disintegrants, fillers and binders. The specific formula is as follows:
the primary disintegrating agent is a mixture of sorbitol, dry starch, natural clay magnesium aluminum silicate and croscarmellose sodium; in the primary disintegrating agent, the mass ratio of the croscarmellose sodium to the dry starch to the natural clay magnesium aluminum silicate to the sorbitol is 1:4:0.5:0.2 in sequence; the secondary disintegrating agent adopts sodium carboxymethyl starch; the ratio of the dosage of the primary disintegrating agent to the dosage of the secondary disintegrating agent is 1: 0.6.
The filler is a mixture of lactose and calcium hydrophosphate, and the mass ratio of the lactose to the calcium hydrophosphate is 3:1 in sequence;
the adhesive is a mixture of syrup, dextrin and high-substituted hydroxypropyl cellulose, and the mass ratio of the syrup, the dextrin and the high-substituted hydroxypropyl cellulose is 1:0.2:0.7 in sequence;
the lubricant is silica gel micropowder.
Example 3
The embodiment provides a preparation process of an amoxicillin dispersible tablet, which comprises the following specific steps:
step 1, respectively crushing an amoxicillin raw drug and auxiliary materials, wherein the crushed particle size of the amoxicillin is 40-60 meshes, and the crushed particle size of the auxiliary materials is 60-80 meshes;
step 2, placing the crushed amoxicillin raw drug and auxiliary materials into a ball mill for ball milling and mixing to prepare a mixture, wherein the particle size of the ball milled mixture is 80-100 meshes;
step 3, adding ethanol into the mixture prepared in the step 2, wherein the ratio of the total mass of the mixture to the mass of the added ethanol is 7; uniformly stirring, tabletting, drying, crushing and screening to obtain a primary molding material, wherein the pressure of tabletting operation is 2.5MPa, and the particle size of the screened material is 40-60 meshes; when the materials are dried, vacuum drying is adopted, the drying temperature is 50 ℃, and the drying time is 5 hours;
step 4, uniformly mixing the crushed secondary disintegrating agent and the lubricant with the particle size of 60-80 meshes with the dried material;
step 5, tabletting;
the mass of the amoxicillin raw drug and the total mass and the mixture ratio of the auxiliary materials, the secondary disintegrating agent and the lubricant are 5.0, specifically, the amoxicillin raw drug is as follows: disintegrant (sum of mass of primary and secondary disintegrants): filling agent: adhesive: the lubricant is 1:0.10:0.07:0.02: 0.01. The auxiliary materials comprise: primary disintegrants, fillers and binders. The specific formula is as follows:
the primary disintegrating agent is a mixture of sorbitol, dry starch, natural clay magnesium aluminum silicate and croscarmellose sodium; in the primary disintegrating agent, the mass ratio of the croscarmellose sodium to the dry starch to the natural clay magnesium aluminum silicate to the sorbitol is 1:4:0.5:0.2 in sequence; the secondary disintegrating agent adopts sodium carboxymethyl starch; the ratio of the dosage of the primary disintegrating agent to the dosage of the secondary disintegrating agent is 1: 0.6.
The filler is a mixture of lactose and calcium hydrophosphate, and the mass ratio of the lactose to the calcium hydrophosphate is 3:1 in sequence;
the adhesive is a mixture of syrup, dextrin and high-substituted hydroxypropyl cellulose, and the mass ratio of the syrup, the dextrin and the high-substituted hydroxypropyl cellulose is 1:0.2:0.7 in sequence;
the lubricant is silica gel micropowder.
Comparative example 1
The comparative example provides a preparation process of amoxicillin dispersible tablets, which has the same specific steps as example 2, and is different from the following steps:
step 3, adding ethanol into the mixture prepared in the step 2, preparing a soft material, granulating and mixing; drying the obtained material, wherein the particle size of the screened material is 40-60 meshes;
comparative example 2
The comparative example provides a preparation process of amoxicillin dispersible tablets, which has the same specific steps as example 2, and is different from the following steps: and (3) simultaneously using the primary disintegrant and the secondary disintegrant as auxiliary materials, crushing in the step (1), and ball-milling and mixing with the amoxicillin raw drug in the step (2).
Comparative example 3
The comparative example provides a preparation process of amoxicillin dispersible tablets, which has the same specific steps as example 2, and is different from the following steps: the primary and secondary disintegrants are mixed with the dried material at the same time in step 4.
Comparative example 4
The comparative example provides a preparation process of amoxicillin dispersible tablets, which has the same specific steps as example 2, and is different from the following steps: the primary disintegrating agent adopts croscarmellose sodium, and the secondary disintegrating agent adopts crospolyvinylpyrrolidone.
Comparative example 5
The comparative example provides a preparation process of amoxicillin dispersible tablets, which has the same specific steps as example 2, and is different from the following steps: the primary disintegrating agent is a mixture of dry starch, natural clay magnesium aluminum silicate and croscarmellose sodium; in the primary disintegrating agent, the mass ratio of the croscarmellose sodium to the dry starch to the natural clay magnesium aluminum silicate to the sorbitol is 1:1:1:1 in sequence.
Comparative example 6
The comparative example provides a preparation process of amoxicillin dispersible tablets, which has the same specific steps as example 2, and is different from the following steps: the filler is lactose.
Comparative example 7
The embodiment provides a preparation process of amoxicillin dispersible tablets, which has the same specific steps as the embodiment 2, and is different from the following steps: the adhesive is a mixture of highly substituted hydroxypropyl cellulose.
Comparative example 8
The comparative example provides a preparation process of amoxicillin dispersible tablets, the formula is the same as that of example 2, and the difference is that:
the amoxicillin raw drug, the primary disintegrant, the secondary disintegrant, the filler, the adhesive and the lubricant are respectively crushed, the crushed particle size of the amoxicillin is 40-60 meshes, the crushed particle size of the other materials is 60-80 meshes, and the crushed materials are mixed uniformly and then directly tabletted.
The amoxicillin dispersible tablets prepared in examples 1-3 and comparative examples 1-8 were tested and the test results are shown in table 1:
TABLE 1 test results of Amoxicillin dispersible tablets prepared in examples 1-3 and comparative examples 1-8
| Sample (I) | Degree of friability | Dissolution rate | Uniformity of dispersion | Appearance of the product |
| Example 1 | 0.09％ | 99.6％ | 31s | Qualified, smooth and crack-free |
| Example 2 | 0.07％ | 99.7％ | 29s | Qualified, smooth and crack-free |
| Example 3 | 0.08％ | 99.6％ | 34s | Qualified, smooth and crack-free |
| Comparative example 1 | 1.0％ | 89.1％ | 1min12s | Qualified, smooth and crack-free |
| Comparative example 2 | 1.0％ | 99.5％ | 44s | Qualified, smooth and crack-free |
| Comparative example 3 | 1.1％ | 99.4％ | 46s | Qualified, smooth and crack-free |
| Comparative example 4 | 1.2％ | 89.9％ | 1min01s | Qualified, smooth and crack-free |
| Comparative example 5 | 1.1％ | 99.3％ | 53s | Qualified, smooth and crack-free |
| Comparative example 6 | 1.3％ | 99.5％ | 45s | Qualified, smooth and crack-free |
| Comparative example 7 | 1.5％ | 99.5％ | 50s | The surface is rough and has no cracks |
| Comparative example 8 | 1.7％ | 99.4％ | 49s | Failure, rough surface, cracks |
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are merely exemplary embodiments of the present invention, and are not intended to limit the scope of the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (6)
1. A preparation process of amoxicillin dispersible tablets is characterized by comprising the following steps:
step 1, respectively crushing an amoxicillin raw material and auxiliary materials;
step 2, placing the crushed amoxicillin raw drug and auxiliary materials into a ball mill for ball milling and mixing to prepare a mixture;
step 3, adding ethanol into the mixture prepared in the step 2, uniformly stirring, and then sequentially tabletting, drying, crushing and screening to obtain a primary molding material;
step 4, mixing the screened material, the secondary disintegrating agent and the lubricant;
step 5, tabletting;
the auxiliary materials are as follows: primary disintegrants, fillers and binders;
the primary disintegrating agent is a mixture of sorbitol, dry starch, natural clay magnesium aluminum silicate and croscarmellose sodium; the secondary disintegrating agent adopts sodium carboxymethyl starch; in the primary disintegrating agent, the mass ratio of the croscarmellose sodium to the dry starch to the natural clay magnesium aluminum silicate to the sorbitol is 1:4:0.5:0.2 in sequence, and the ratio of the amount of the primary disintegrating agent to the amount of the secondary disintegrating agent is 1: 0.6;
the filler is a mixture of lactose and calcium hydrophosphate, and the mass ratio of the lactose to the calcium hydrophosphate is 3:1 in sequence; the adhesive is a mixture of syrup, dextrin and high-substituted hydroxypropyl cellulose, and the mass ratio of the syrup, the dextrin and the high-substituted hydroxypropyl cellulose is 1:0.2:0.7 in sequence; the lubricant is micropowder silica gel;
the ratio of the amoxicillin technical material to the auxiliary material in the step 1 and the secondary disintegrant and lubricant in the step 4 is 3.5-5.0.
2. The preparation process of amoxicillin dispersible tablets according to claim 1, characterized in that in step 1, the crushed amoxicillin has a particle size of 40-60 meshes, and the crushed adjuvant has a particle size of 60-80 meshes; in the step 2, the particle size of the mixture after ball milling is 80-100 meshes.
3. The process for preparing amoxicillin dispersible tablets according to claim 1, wherein in step 3, the ratio of the total mass of the mixture to the mass of the added ethanol is 5 to 7.
4. The process for preparing amoxicillin dispersible tablets according to claim 3, wherein the tabletting operation in step 3 is performed under a pressure of 1.8-2.5 MPa, and the particle size of the sieved material is 40-60 mesh.
5. The preparation process of amoxicillin dispersible tablets according to claim 1, characterized in that in step 3, vacuum drying is adopted, the drying temperature is 35-50 ℃, and the drying time is 5-10 h.
6. The preparation process of amoxicillin dispersible tablets according to claim 1, characterized in that in step 4, the secondary disintegrant and lubricant with particle size of 60-80 mesh after pulverization are mixed uniformly with the sieved material.
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| CN104161734A (en) * | 2014-09-04 | 2014-11-26 | 海口市制药厂有限公司 | Amoxicillin dispersible tablet as well as preparation method and use thereof |
| CN107019677A (en) * | 2017-04-26 | 2017-08-08 | 四川制药制剂有限公司 | The preparation method of amoxicillin dispersible tablet |
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| CN104161734A (en) * | 2014-09-04 | 2014-11-26 | 海口市制药厂有限公司 | Amoxicillin dispersible tablet as well as preparation method and use thereof |
| CN107019677A (en) * | 2017-04-26 | 2017-08-08 | 四川制药制剂有限公司 | The preparation method of amoxicillin dispersible tablet |
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