CN113456603A - Preparation method of lamotrigine dispersible tablets - Google Patents
Preparation method of lamotrigine dispersible tablets Download PDFInfo
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- CN113456603A CN113456603A CN202110753444.2A CN202110753444A CN113456603A CN 113456603 A CN113456603 A CN 113456603A CN 202110753444 A CN202110753444 A CN 202110753444A CN 113456603 A CN113456603 A CN 113456603A
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- lamotrigine
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- auxiliary materials
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- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 229960001848 lamotrigine Drugs 0.000 title claims abstract description 52
- 239000007919 dispersible tablet Substances 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000000463 material Substances 0.000 claims abstract description 23
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 22
- 238000002156 mixing Methods 0.000 claims abstract description 22
- 239000002994 raw material Substances 0.000 claims abstract description 20
- 238000001035 drying Methods 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 10
- 108010011485 Aspartame Proteins 0.000 claims abstract description 9
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 9
- 229930195725 Mannitol Natural products 0.000 claims abstract description 9
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 9
- 229920002472 Starch Polymers 0.000 claims abstract description 9
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims abstract description 9
- 235000010357 aspartame Nutrition 0.000 claims abstract description 9
- 239000000605 aspartame Substances 0.000 claims abstract description 9
- 229960003438 aspartame Drugs 0.000 claims abstract description 9
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims abstract description 9
- 229960000913 crospovidone Drugs 0.000 claims abstract description 9
- 239000000594 mannitol Substances 0.000 claims abstract description 9
- 235000010355 mannitol Nutrition 0.000 claims abstract description 9
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 9
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 9
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 9
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims abstract description 9
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims abstract description 9
- 239000011734 sodium Substances 0.000 claims abstract description 9
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 9
- 239000008107 starch Substances 0.000 claims abstract description 9
- 235000019698 starch Nutrition 0.000 claims abstract description 9
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical group CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000007968 orange flavor Substances 0.000 claims abstract description 8
- 239000000853 adhesive Substances 0.000 claims abstract description 7
- 230000001070 adhesive effect Effects 0.000 claims abstract description 7
- 238000005469 granulation Methods 0.000 claims abstract description 6
- 230000003179 granulation Effects 0.000 claims abstract description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 15
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 13
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 13
- 229940069328 povidone Drugs 0.000 claims description 13
- 239000008187 granular material Substances 0.000 claims description 12
- 239000011230 binding agent Substances 0.000 claims description 10
- 238000005303 weighing Methods 0.000 claims description 10
- 235000019359 magnesium stearate Nutrition 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 238000005520 cutting process Methods 0.000 claims description 5
- 239000008213 purified water Substances 0.000 claims description 5
- 238000007873 sieving Methods 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000012535 impurity Substances 0.000 abstract description 5
- 230000015556 catabolic process Effects 0.000 abstract description 4
- 238000006731 degradation reaction Methods 0.000 abstract description 4
- 239000006185 dispersion Substances 0.000 abstract description 4
- 239000003205 fragrance Substances 0.000 abstract description 3
- 239000007767 bonding agent Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 4
- 206010015037 epilepsy Diseases 0.000 description 4
- 206010010904 Convulsion Diseases 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 230000003556 anti-epileptic effect Effects 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 208000028329 epileptic seizure Diseases 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 206010012374 Depressed mood Diseases 0.000 description 1
- 208000001654 Drug Resistant Epilepsy Diseases 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- 108010052164 Sodium Channels Proteins 0.000 description 1
- 102000018674 Sodium Channels Human genes 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000007781 pre-processing Methods 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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Abstract
The invention discloses a preparation method of lamotrigine dispersible tablets, which comprises the following steps: s1: pretreating raw materials and auxiliary materials; s2: preparing an adhesive; s3: adding a bonding agent for granulation; s4: drying and granulating; s5: totally mixing; s6: and (6) tabletting. The raw materials and auxiliary materials comprise the following components in percentage by weight: lamotrigine 39.4%, mannitol 27.6%, microcrystalline cellulose 23.7%, carboxymethyl starch sodium 3.9%, crospovidone 1.6%, aspartame 1.0% and orange essence 1.0%. The lamotrigine dispersible tablet prepared by the method has no obvious difference with the original preparation in appearance, friability and dispersion uniformity, and the fragrance is orange flavor and is more easily accepted; and the lamotrigine dispersible tablet has high stability and does not contain degradation impurities in the long-time placing process.
Description
Technical Field
The invention relates to the technical field of medicine processing, in particular to a preparation method of lamotrigine dispersible tablets.
Background
Lamotrigine is a white or off-white powder, slightly soluble in water, melting point 216-. Pharmacological results suggest that lamotrigine is a use-dependent blocker of voltage-gated sodium ion channels. Lamotrigine, which is responsible for sustained repetitive firing of cultured neuronal cells, produces a use-dependent and voltage-dependent block that inhibits pathological glutamate release, which is critical for seizure formation, and also inhibits glutamate-induced motor potential bursts.
The lamotrigine dispersible tablet is a prescription drug, and the original preparation is sold as 'libitong'. It has the function of mainly treating intractable epilepsy, and can be used alone or as additive therapy, or be used for treating epileptic seizure combined with comprehensive Calstorynox syndrome. Is one of the most ideal medicines for treating epilepsy in the market at present. As single medicine treatment, the lamotrigine dispersible tablet is a broad-spectrum, high-efficiency and safe antiepileptic medicine. Compared with similar antiepileptic drugs, the lamotrigine dispersible tablet has more advantages, can meet different age groups, is suitable for more audiences, can effectively inhibit epileptic seizure, and has the advantages of low toxicity, less adverse effect, convenient administration and strong patient compliance. Lamotrigine is mainly used for anti-epileptic effect, is a first choice drug for treating bipolar disorder by improving mood depression, and is used for assisting in treating schizophrenia by stabilizing the non-activated state of a channel and relieving extrapyramidal reactions. Lamotrigine has certain antianxiety effect, and is helpful for treating depression and anxiety disorder of heroin dependent patients.
The existing lamotrigine dispersible tablets have poor mouthfeel after dispersion, and are inconvenient for patients to take; meanwhile, the existing lamotrigine dispersible tablets have high preparation difficulty, high technical requirements on operators and high residue rate, and are not suitable for large-scale production.
Disclosure of Invention
The invention aims to provide a preparation method of lamotrigine dispersible tablets, and the lamotrigine dispersible tablets prepared by the method have the advantages of simple preparation, high stability, good taste and convenient administration, and are used for solving the technical problems in the background technology.
The invention discloses a preparation method of lamotrigine dispersible tablets, which comprises the following steps:
s1: pretreating raw materials and auxiliary materials, weighing the following components in percentage by weight: 39-39.4 wt% of lamotrigine, 27.6-28 wt% of mannitol, 23-23.7 wt% of microcrystalline cellulose, 3.9-4.6 wt% of carboxymethyl starch sodium, 1.6-2 wt% of crospovidone, 0.8-1 wt% of aspartame, 1-1.1 wt% of orange flavor essence, and mixing and sieving raw materials and auxiliary materials;
s2: preparing an adhesive, weighing 0.4-0.8 wt% of povidone, and adding purified water until the povidone is completely dissolved;
s3: adding a binder for granulation, adding the raw and auxiliary materials of S1 into a wet granulator with a screen mesh for mixing and stirring, adding the binder obtained in S2, stirring and cutting to obtain wet granules;
s4: drying and granulating, namely pouring wet granules into a fluidized bed for drying, and granulating by a granulator with a screen;
s5: mixing, adding 1-1.1 wt% magnesium stearate into the whole granule, mixing and stirring;
s6: and (4) tabletting, namely tabletting and drying the raw material obtained in the step S5 to obtain the lamotrigine dispersible tablet.
In a preferred embodiment, the raw and auxiliary materials comprise the following components in percentage by weight: lamotrigine 39.4%, mannitol 27.6%, microcrystalline cellulose 23.7%, carboxymethyl starch sodium 3.9%, crospovidone 1.6%, aspartame 1.0% and orange essence 1.0%.
In a preferred embodiment, said povidone is 0.8 wt%, said magnesium stearate is 1 wt%.
In a preferred embodiment, the screen mesh size screened in S1 is 50 mesh, the screen mesh size of the wet granulator in S3 is 24 mesh, and the mesh size of the granulator screen in S4 is 30 mesh.
In a preferred embodiment, the monolithic mass of the lamotrigine dispersible tablet obtained in S6 is 126-127 mg.
The technical scheme of the invention has the beneficial effects that:
the following raw materials are adopted as raw and auxiliary materials: lamotrigine, mannitol, microcrystalline cellulose, carboxymethyl starch sodium, crospovidone, aspartame and orange flavor essence, wherein the orange flavor essence ensures the taste of the prepared dispersible tablet and is better to enter the mouth compared with the original developed product. And the raw and auxiliary materials are sieved during mixing, so that the phenomena of caking and the like of the raw and auxiliary materials are avoided. Povidone is adopted as an adhesive to bond the raw and auxiliary materials, and the success rate of tabletting is ensured by adding magnesium stearate.
The lamotrigine dispersible tablet prepared by the method has no obvious difference with the original preparation in appearance, friability and dispersion uniformity, and the fragrance is orange flavor and is more easily accepted; and the lamotrigine dispersible tablet has high stability and does not contain degradation impurities in the long-time placing process.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments. The embodiments of the present invention have been presented for purposes of illustration and description, and are not intended to be exhaustive or limited to the invention in the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art. The embodiment was chosen and described in order to best explain the principles of the invention and the practical application, and to enable others of ordinary skill in the art to understand the invention for various embodiments with various modifications as are suited to the particular use contemplated.
Example 1
The invention discloses a preparation method of lamotrigine dispersible tablets, which comprises the following steps:
s1: preprocessing raw and auxiliary materials, weighing 39.4 percent of lamotrigine, 27.6 percent of mannitol, 23.7 percent of microcrystalline cellulose, 3.9 percent of carboxymethyl starch sodium, 1.6 percent of crospovidone, 1.0 percent of aspartame and 1.0 percent of orange flavor by weight percent, mixing and sieving the raw and auxiliary materials;
s2: preparing an adhesive, weighing 0.8 wt% of povidone, and adding purified water until the povidone is completely dissolved;
s3: adding a binder for granulation, adding the raw and auxiliary materials of S1 into a wet granulator with a screen mesh for mixing and stirring, adding the binder obtained in S2, stirring and cutting to obtain wet granules;
s4: drying and granulating, namely pouring wet granules into a fluidized bed for drying, and granulating by a granulator with a screen;
s5: mixing, namely adding 1 wt% of magnesium stearate into the whole granulated raw materials, mixing and stirring;
s6: and (4) tabletting, namely tabletting and drying the raw material obtained in the step S5 to obtain the lamotrigine dispersible tablet.
The mesh number of the screen sieved in the S1 is 50 meshes, the mesh number of the screen of the wet granulator in the S3 is 24 meshes, and the mesh number of the screen of the granulator in the S4 is 30 meshes.
The monolithic mass of the lamotrigine dispersible tablet obtained in S6 was 126.75.
Example 2
The invention discloses a preparation method of lamotrigine dispersible tablets, which comprises the following steps:
s1: pretreating raw materials and auxiliary materials, weighing the following components in percentage by weight: 39 wt% of lamotrigine, 28 wt% of mannitol, 23 wt% of microcrystalline cellulose, 4.6 wt% of carboxymethyl starch sodium, 1.6 wt% of crospovidone, 0.8 wt% of aspartame and 1.1 wt% of orange-flavored essence, and mixing and sieving the raw materials and the auxiliary materials;
s2: preparing an adhesive, weighing 0.8 wt% of povidone, and adding purified water until the povidone is completely dissolved;
s3: adding a binder for granulation, adding the raw and auxiliary materials of S1 into a wet granulator with a screen mesh for mixing and stirring, adding the binder obtained in S2, stirring and cutting to obtain wet granules;
s4: drying and granulating, namely pouring wet granules into a fluidized bed for drying, and granulating by a granulator with a screen;
s5: mixing, namely adding 1.1 wt% of magnesium stearate into the whole granulated raw materials, mixing and stirring;
s6: and (4) tabletting, namely tabletting and drying the raw material obtained in the step S5 to obtain the lamotrigine dispersible tablet.
The mesh number of the screen sieved in the S1 is 50 meshes, the mesh number of the screen of the wet granulator in the S3 is 24 meshes, and the mesh number of the screen of the granulator in the S4 is 30 meshes.
The mass of the lamotrigine dispersible tablet obtained in S6 was 126 mg.
Example 3
The invention discloses a preparation method of lamotrigine dispersible tablets, which comprises the following steps:
s1: pretreating raw materials and auxiliary materials, weighing the following components in percentage by weight: 39.4 wt% of lamotrigine, 28 wt% of mannitol, 23.7 wt% of microcrystalline cellulose, 3.9 wt% of carboxymethyl starch sodium, 2 wt% of crospovidone, 1 wt% of aspartame and 1 wt% of orange-flavored essence, and mixing and sieving the raw materials and the auxiliary materials;
s2: preparing an adhesive, weighing 0.4 wt% of povidone, and adding purified water until the povidone is completely dissolved;
s3: adding a binder for granulation, adding the raw and auxiliary materials of S1 into a wet granulator with a screen mesh for mixing and stirring, adding the binder obtained in S2, stirring and cutting to obtain wet granules;
s4: drying and granulating, namely pouring wet granules into a fluidized bed for drying, and granulating by a granulator with a screen;
s5: mixing, namely adding 1 wt% of magnesium stearate into the whole granulated raw materials, mixing and stirring;
s6: and (4) tabletting, namely tabletting and drying the raw material obtained in the step S5 to obtain the lamotrigine dispersible tablet.
The mesh number of the screen sieved in the S1 is 50 meshes, the mesh number of the screen of the wet granulator in the S3 is 24 meshes, and the mesh number of the screen of the granulator in the S4 is 30 meshes.
The mass of the lamotrigine dispersible tablet obtained in S6 was 127mg in a single tablet.
The lamotrigine dispersible tablets prepared in examples 1-3 were tested against the original formulation and the results are shown in the following table one:
watch 1
As can be seen from the table I, the lamotrigine dispersible tablets prepared by the invention have no obvious difference in appearance, friability and dispersion uniformity and the original preparation, and the fragrance is orange flavor and is more easily accepted.
The lamotrigine dispersible tablets prepared in examples 1-3 were compared with the original formulation in stability studies at 30 + -2 deg.C and 65 + -5% humidity for the key impurity A (degradation impurity) with the following results:
| sample name | 0 month | 3 month | 6 month | 9 month | 12 month |
| Example 1 | Not detected out | Not detected out | Not detected out | Not detected out | Not detected out |
| Example 2 | Not detected out | Not detected out | Not detected out | Not detected out | Not detected out |
| Example 3 | Not detected out | Not detected out | Not detected out | Not detected out | Not detected out |
| Original product for grinding | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 |
TABLE 2
As can be seen from the table two, the lamotrigine dispersible tablets prepared by the invention have high stability, and no degradation impurity is detected in the long-time standing process.
It is to be understood that the described embodiments are merely a few embodiments of the invention, and not all embodiments. All other embodiments, which can be derived by one of ordinary skill in the art and related arts based on the embodiments of the present invention without any creative effort, shall fall within the protection scope of the present invention. Structures, devices, and methods of operation not specifically described or illustrated herein are generally practiced in the art without specific recitation or limitation.
Claims (5)
1. A preparation method of lamotrigine dispersible tablets is characterized by comprising the following steps:
s1: pretreating raw materials and auxiliary materials, weighing the following components in percentage by weight: 39-39.4 wt% of lamotrigine, 27.6-28 wt% of mannitol, 23-23.7 wt% of microcrystalline cellulose, 3.9-4.6 wt% of carboxymethyl starch sodium, 1.6-2 wt% of crospovidone, 0.8-1 wt% of aspartame, 1-1.1 wt% of orange flavor essence, and mixing and sieving raw materials and auxiliary materials;
s2: preparing an adhesive, weighing 0.4-0.8 wt% of povidone, and adding purified water until the povidone is completely dissolved;
s3: adding a binder for granulation, adding the raw and auxiliary materials of S1 into a wet granulator with a screen mesh for mixing and stirring, adding the binder obtained in S2, stirring and cutting to obtain wet granules;
s4: drying and granulating, namely pouring wet granules into a fluidized bed for drying, and granulating by a granulator with a screen;
s5: mixing, adding 1-1.1 wt% magnesium stearate into the whole granule, mixing and stirring;
s6: and (4) tabletting, namely tabletting and drying the raw material obtained in the step S5 to obtain the lamotrigine dispersible tablet.
2. The preparation method of lamotrigine dispersible tablet according to claim 1, wherein the weight percentage of the raw materials and auxiliary materials is: lamotrigine 39.4%, mannitol 27.6%, microcrystalline cellulose 23.7%, carboxymethyl starch sodium 3.9%, crospovidone 1.6%, aspartame 1.0% and orange essence 1.0%.
3. The method for preparing lamotrigine dispersible tablets according to claim 1, wherein povidone is 0.8 wt% and magnesium stearate is 1 wt%.
4. The process for preparing lamotrigine dispersible tablets according to claim 1, wherein the mesh number of the screen sieved in S1 is 50 mesh, the mesh number of the screen of the wet process granulator in S3 is 24 mesh, and the mesh number of the screen of the granulator in S4 is 30 mesh.
5. The method for preparing lamotrigine dispersible tablets as claimed in claim 1, wherein the monolithic mass of lamotrigine dispersible tablet obtained in S6 is 126-127 mg.
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| WO2009006516A1 (en) * | 2007-07-02 | 2009-01-08 | Eurand, Inc. | Orally disintegrating tablet compositions of lamotrigine |
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| WO2009006516A1 (en) * | 2007-07-02 | 2009-01-08 | Eurand, Inc. | Orally disintegrating tablet compositions of lamotrigine |
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