CN112137971A - Orally disintegrating tablet of choline alfoscerate and preparation method thereof - Google Patents
Orally disintegrating tablet of choline alfoscerate and preparation method thereof Download PDFInfo
- Publication number
- CN112137971A CN112137971A CN201910576343.5A CN201910576343A CN112137971A CN 112137971 A CN112137971 A CN 112137971A CN 201910576343 A CN201910576343 A CN 201910576343A CN 112137971 A CN112137971 A CN 112137971A
- Authority
- CN
- China
- Prior art keywords
- mixing
- choline alfoscerate
- prescription amount
- microcrystalline cellulose
- silicon dioxide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000008777 Glycerylphosphorylcholine Substances 0.000 title claims abstract description 54
- SUHOQUVVVLNYQR-MRVPVSSYSA-O glycerylphosphorylcholine Chemical compound C[N+](C)(C)CCO[P@](O)(=O)OC[C@H](O)CO SUHOQUVVVLNYQR-MRVPVSSYSA-O 0.000 title claims abstract description 54
- 229960004788 choline alfoscerate Drugs 0.000 title claims abstract description 52
- 239000006191 orally-disintegrating tablet Substances 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 52
- GUBGYTABKSRVRQ-UHFFFAOYSA-N 2-(hydroxymethyl)-6-[4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol Chemical compound OCC1OC(OC2C(O)C(O)C(O)OC2CO)C(O)C(O)C1O GUBGYTABKSRVRQ-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 26
- 229920002785 Croscarmellose sodium Polymers 0.000 claims abstract description 25
- 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 abstract description 25
- 229960001681 croscarmellose sodium Drugs 0.000 claims abstract description 25
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims abstract description 25
- 235000012239 silicon dioxide Nutrition 0.000 claims abstract description 25
- 239000000945 filler Substances 0.000 claims abstract description 13
- 239000000314 lubricant Substances 0.000 claims abstract description 13
- 239000000796 flavoring agent Substances 0.000 claims abstract description 12
- 235000013355 food flavoring agent Nutrition 0.000 claims abstract description 12
- 229960001866 silicon dioxide Drugs 0.000 claims abstract description 11
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 36
- 239000008187 granular material Substances 0.000 claims description 25
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 20
- 229930195725 Mannitol Natural products 0.000 claims description 20
- 239000000594 mannitol Substances 0.000 claims description 20
- 235000010355 mannitol Nutrition 0.000 claims description 20
- 239000003826 tablet Substances 0.000 claims description 19
- 235000019359 magnesium stearate Nutrition 0.000 claims description 18
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 18
- 239000004376 Sucralose Substances 0.000 claims description 17
- 235000019408 sucralose Nutrition 0.000 claims description 17
- 238000007873 sieving Methods 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 6
- 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 4
- 229920002472 Starch Polymers 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 108010011485 Aspartame Proteins 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- 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 description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 2
- 235000003599 food sweetener Nutrition 0.000 claims description 2
- 229940049654 glyceryl behenate Drugs 0.000 claims description 2
- 229940057948 magnesium stearate Drugs 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 229960004274 stearic acid Drugs 0.000 claims description 2
- 229940013618 stevioside Drugs 0.000 claims description 2
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims description 2
- 235000019202 steviosides Nutrition 0.000 claims description 2
- 239000003765 sweetening agent Substances 0.000 claims description 2
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims 1
- 235000010358 acesulfame potassium Nutrition 0.000 claims 1
- 229960004998 acesulfame potassium Drugs 0.000 claims 1
- 239000000619 acesulfame-K Substances 0.000 claims 1
- 239000004067 bulking agent Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 6
- 239000000843 powder Substances 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract description 2
- 230000008569 process Effects 0.000 abstract description 2
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 abstract 1
- 229960004372 aripiprazole Drugs 0.000 abstract 1
- 238000007907 direct compression Methods 0.000 abstract 1
- 235000019640 taste Nutrition 0.000 description 8
- 239000000126 substance Substances 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 208000019505 Deglutition disease Diseases 0.000 description 2
- 230000001055 chewing effect Effects 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000003962 counterfeit drug Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 229960004956 glycerylphosphorylcholine Drugs 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000005314 Multi-Infarct Dementia Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 201000004559 cerebral degeneration Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 description 1
- 150000003904 phospholipids Chemical group 0.000 description 1
- 229950004354 phosphorylcholine Drugs 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229940126532 prescription medicine Drugs 0.000 description 1
- 239000003368 psychostimulant agent Substances 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 230000004580 weight loss Effects 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
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hospice & Palliative Care (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Psychiatry (AREA)
- Inorganic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a choline alfoscerate orally disintegrating tablet and a preparation method thereof, wherein the choline alfoscerate orally disintegrating tablet comprises active ingredients of aripiprazole, silicified microcrystalline cellulose, croscarmellose sodium, silicon dioxide, a filler, a flavoring agent and a lubricant, and is prepared by a powder direct compression process on the basis of the formula.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to an orally disintegrating tablet of choline alfoscerate and a preparation method thereof.
Background
Choline alfoscerate is a psychostimulant and activates the central nervous system of elderly patients, and contains choline and phosphorylcholine precursors. It can be effectively used for preventing and treating biochemical pathological changes. It can clearly identify the pathological factors of various symptoms caused by organ degeneration, thereby reducing choline tone and changing phospholipid structure of the neural mucosa. Unlike other choline forms, choline alfoscerate normally enters the blood brain barrier more readily. The chemical structure and the related chemical and physical properties of the glyceryl phosphorylcholine provide sufficient nutrients for protecting brain tissues to complete normal metabolism. The results of pharmacological tests and clinical studies confirm that glyceryl phosphorylcholine has incomparable and strong intervention capability on cognitive function and memory function when aiming at emotional and behavioral abnormalities caused by brain degeneration. The composition is clinically used for treating patients with ischemic attack (stroke or transient ischemic attack) within 10 days, mild to moderate Alzheimer dementia and multi-infarct dementia. Is a good medicine for protecting liver and a prescription medicine for treating senile dementia.
The choline alfoscerate preparation on the market at present mainly takes soft capsules and tablets as main materials, has low disintegration speed, is not suitable for patients with dysphagia or special conditions to take, and is a common problem for patients with Alzheimer's disease because the choline alfoscerate preparation is often accompanied with dysphagia or ' fake medicine '. In order to facilitate patients, solve the practical problems in treatment, develop the orally disintegrating tablet with the advantages of high disintegration speed, high drug effect exertion and the like, can effectively improve the compliance of patients, and can disintegrate in the oral cavity to solve the problem of 'fake medicine' of mental patients, but some problems are not solved, such as poor taste, obvious reduction of dissolution after long-term placement, obvious reduction of curative effect, obvious increase of related substances and the like.
The silicified microcrystalline cellulose is used as one of main fillers of the choline alfoscerate orally disintegrating tablet, so that smooth and fine mouthfeel is brought, the problem of granular sensation of the orally disintegrating tablet is solved, the long-term dissolution rate of the preparation is improved, and related substances with toxic and side effects are reduced. More surprisingly, in order to improve the dissolution stability and the chemical stability, the choline alfoscerate orally disintegrating tablet containing silicified microcrystalline cellulose is produced by adopting an improved process, the taste acceptance is better, the dissolution change after the orally disintegrating tablet is placed for a long time is smaller, the related substances are increased less, the curative effect is ensured, and the safety is improved.
Disclosure of Invention
In order to solve some key problems still existing in the prior art, the invention provides the choline alfoscerate orally disintegrating tablet formula with excellent taste and better long-term stability and the preparation process thereof, the stability of the obtained product is obviously improved, and the effectiveness and the safety of the medicine after long-term storage are better guaranteed.
The choline alfoscerate orally disintegrating tablet comprises choline alfoscerate serving as an active ingredient, silicified microcrystalline cellulose, croscarmellose sodium, silicon dioxide, a filler, a flavoring agent and a lubricant;
wherein the choline alfoscerate accounts for 5 to 10 percent by weight
Wherein the silicified microcrystalline cellulose accounts for 30-67% by weight
Wherein the weight percentage of the croscarmellose sodium is 3-5%
Wherein the weight percentage of the silicon dioxide is 0.8 to 1.5 percent
Wherein the weight percentage of the filler is 14 to 62 percent
Wherein the weight percentage of the flavoring agent is 0.2-1.0%
Wherein the weight percentage of the lubricant is 0.5-1.5%
The choline alfoscerate orally disintegrating tablet of the present invention has the filler selected from one or more of lactose, mannitol, starch lactose complex and mannitol starch complex, preferably mannitol.
The choline alfoscerate orally disintegrating tablet of the invention is characterized in that the sweetener is selected from one or more of aspartame, sucralose and stevioside, and sucralose is preferred.
The choline alfoscerate orally disintegrating tablet of the present invention comprises one or more lubricants selected from magnesium stearate, stearic acid, sodium stearyl fumarate, and glyceryl behenate, preferably magnesium stearate.
The choline alfoscerate orally disintegrating tablet of the invention has the following preparation method steps:
(1) mixing the prescription dose of choline alfoscerate, filler, silicified microcrystalline cellulose, croscarmellose sodium, silicon dioxide and flavoring agent;
(2) and (3) adding the lubricant with the prescription amount into the mixed granules prepared in the step (1), mixing and tabletting to obtain the finished product.
The invention provides choline alfoscerate orally disintegrating tablets, which preferably comprises the following steps:
1) mixing the prescription dose of choline alfoscerate with silicon dioxide, and sieving twice with a 100-mesh and 200-mesh sieve
2) Adding the prescribed amount of filler, silicified microcrystalline cellulose, croscarmellose sodium and flavoring agent into the mixed granules prepared in the step (1) and mixing;
(3) and (3) adding the lubricant with the prescription amount into the mixed granules prepared in the step (2), mixing and tabletting to obtain the finished product.
The invention provides choline alfoscerate orally disintegrating tablets, which preferably comprises the following steps:
(1) mixing the prescription dose of choline alfoscerate with silicon dioxide, and sieving with a 100-200 mesh sieve twice;
(2) taking the prescribed amount of filler, silicified microcrystalline cellulose, croscarmellose sodium and flavoring agent to be added in the step
(3) And (3) adding the lubricant with the prescription amount into the mixed granules prepared in the step (2), mixing and tabletting to obtain the finished product.
The choline alfoscerate orally disintegrating tablet further comprises the following components in percentage by weight:
5 to 10 percent of choline alfoscerate
14 to 62 percent of mannitol
Silicified microcrystalline cellulose 30-67%
3-5% of croscarmellose sodium
0.8 to 1.5 percent of silicon dioxide
0.2 to 1.0 percent of sucralose
Magnesium stearate 0.5-1.5%
The choline alfoscerate orally disintegrating tablet further comprises the following components in percentage by weight:
5 to 10 percent of choline alfoscerate
38 to 50 percent of mannitol
Silicified microcrystalline cellulose 40-50%
3-5% of croscarmellose sodium
0.8 to 1.5 percent of silicon dioxide
0.2 percent of sucralose
Magnesium stearate 0.5-0.7%
The preparation method of the choline alfoscerate orally disintegrating tablet comprises the following steps of (1) mixing prescription dose of choline alfoscerate, mannitol, silicified microcrystalline cellulose, croscarmellose sodium, silicon dioxide and sucralose, (2) adding prescription dose of magnesium stearate into the mixed granules prepared in the step (1), mixing and tabletting.
The invention provides choline alfoscerate orally disintegrating tablets, which preferably comprises the following steps:
1) mixing the prescription dose of choline alfoscerate with silicon dioxide, and sieving twice with a 100-mesh and 200-mesh sieve
2) Adding mannitol, silicified microcrystalline cellulose, croscarmellose sodium and a flavoring agent in the formula amount into the mixed granules prepared in the step (1) and mixing;
(3) and (3) adding the magnesium stearate with the prescription amount into the mixed granules prepared in the step (2), mixing and tabletting to obtain the tablet.
The choline alfoscerate orally disintegrating tablet of the invention is further optimized in preparation method steps of (1) mixing choline alfoscerate with silicon dioxide according to prescription amount, sieving twice with 100-200 mesh sieve, and (2) adding silicified microcrystalline cellulose according to prescription amount into the granules prepared in the step (1) and mixing. (3) Adding the prescription dose of mannitol, croscarmellose sodium and sucralose into the mixture prepared in the step (2)
(4) And (4) adding the magnesium stearate with the prescription amount into the mixed granules prepared in the step (3), mixing and tabletting to obtain the tablet.
Compared with the prior art, the choline alfoscerate orally disintegrating tablet solves the problem of poor taste in the prior art, has better taste acceptance, and improves the medicine taking experience of patients.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The following detailed description of specific embodiments of the present invention is provided to illustrate and explain the present invention and to be understood not to limit the present invention.
The choline alfoscerate in the following embodiments is the same lot, and the index measurement method for all samples is as follows:
the disintegration time limit measuring method of the invention refers to 0921 of the four-part general rules of 2015 edition of Chinese pharmacopoeia.
The friability measuring method comprises the steps of taking 6.5g of the product, blowing off powder falling off from tablets by using a blower, precisely weighing, placing the product in a cylinder of a friability tester, rotating for 100 times, taking out the product, picking out broken, cracked and crushed tablets, removing the powder by the same method, precisely weighing, and calculating weight loss reduction amount.
The method for measuring the difference of tablet weights comprises the steps of taking 20 tablets of the product, precisely weighing the total weight, obtaining the average tablet weight, precisely weighing the weight of each tablet, and comparing the weight of each tablet with the average tablet weight.
The taste evaluation method comprises the following steps of selecting 6 healthy volunteers without oral inflammation, and gargling with a small amount of purified water before testing. The tablets were taken and 1 tablet was put on the tongue (no water was needed, no chewing was needed) for taste evaluation of each prescription.
The oral cavity disintegration time and taste are evaluated by rinsing with a small amount of purified water before the test. 1 tablet was placed on the tongue (no water and no chewing) and a timer was started, and after completion, each volunteer evaluated the grittiness (rating: -none, + light, + clear, + severe) and bitterness (rating: -none, + slightly bitter, + moderately bitter, + extremely bitter) in all directions.
The preparation method comprises the following steps:
(1) taking prescription dose of choline alfoscerate, mannitol, microcrystalline cellulose, croscarmellose sodium, silicon dioxide and sucralose to mix in a three-dimensional mixer for 20 minutes;
2) and (3) adding the magnesium stearate with the prescription amount into the mixed granules prepared in the step (1), mixing for 5 minutes, and tabletting to obtain the tablet.
Example 1
The preparation method comprises (1) mixing prescription dose of choline alfoscerate, mannitol, silicified microcrystalline cellulose, croscarmellose sodium, silicon dioxide and sucralose in a three-dimensional mixer for 20 minutes;
(2) and (3) adding the magnesium stearate with the prescription amount into the mixed granules prepared in the step (1), mixing for 5 minutes, and tabletting to obtain the tablet.
Example 2
(1) Taking prescription dose of choline alfoscerate, mannitol, silicified microcrystalline cellulose, croscarmellose sodium, silicon dioxide and sucralose to mix in a three-dimensional mixer for 20 minutes;
(2) and (3) adding the magnesium stearate with the prescription amount into the mixed granules prepared in the step (1), mixing for 5 minutes, and tabletting to obtain the tablet.
Example 3
Comparative examples
(1) Taking prescription dose of choline alfoscerate, mannitol, silicified microcrystalline cellulose, croscarmellose sodium, silicon dioxide and sucralose to mix in a three-dimensional mixer for 20 minutes;
(2) and (3) adding the magnesium stearate with the prescription amount into the mixed granules prepared in the step (1), mixing for 5 minutes, and tabletting to obtain the tablet.
The test results for the samples prepared according to the above comparative examples and examples are as follows:
Claims (8)
1. an orally disintegrating tablet containing choline alfoscerate is characterized by comprising the following components of choline alfoscerate, silicified microcrystalline cellulose, croscarmellose sodium, silicon dioxide, a filling agent, a flavoring agent and a lubricant.
2. The orally disintegrating tablet of claim 1, wherein the weight percentage of choline alfoscerate is 5-10%, the weight percentage of silicified microcrystalline cellulose is 30-67%, the weight percentage of croscarmellose sodium is 3-5%, the weight percentage of silicon dioxide is 0.8-1.5%, the weight percentage of filler is 14-62%, the weight percentage of flavoring agent is 0.2-1.0%, and the weight percentage of lubricant is 0.5-1.5%.
3. The orally disintegrating tablet of claim 1, wherein the bulking agent is selected from one or more of lactose, mannitol, starch lactose complex, mannitol starch complex, preferably mannitol, the sweetening agent is selected from one or more of aspartame, sucralose, acesulfame potassium, stevioside, preferably sucralose, and the lubricating agent is selected from one or more of magnesium stearate, stearic acid, sodium stearyl fumarate, glyceryl behenate, preferably magnesium stearate.
4. The orally disintegrating tablet according to any one of claims 1 to 3, wherein the preparation process comprises the steps of:
(1) mixing the prescription dose of choline alfoscerate, filler, silicified microcrystalline cellulose, croscarmellose sodium, silicon dioxide and flavoring agent;
(2) adding a prescription amount of lubricant into the mixed granules prepared in the step (1), mixing, and tabletting to obtain the finished product;
the preferable preparation method comprises the following steps of (1) mixing choline alfoscerate with a prescription amount with silicon dioxide, and sieving the mixture twice with a 100-200-mesh sieve, (2) adding a filling agent with a prescription amount, silicified microcrystalline cellulose, croscarmellose sodium and a flavoring agent into the mixed granules prepared in the step (1) for mixing, (3) adding a lubricating agent with a prescription amount into the mixed granules prepared in the step (2), mixing and tabletting to obtain the compound premix;
the preparation method further comprises the following steps of (1) mixing choline alfoscerate with a prescription amount with silicon dioxide, and sieving the mixture twice with a 100-200-mesh sieve, (2) adding silicified microcrystalline cellulose with the prescription amount into the granules prepared in the step (1) and mixing;
(3) adding the prescription amount of filling agent, the croscarmellose sodium and the flavoring agent into the mixed granules prepared in the step (2) for mixing, and (4) adding the prescription amount of lubricant into the mixed granules prepared in the step (3), mixing and tabletting to obtain the tablet.
5. The orally disintegrating tablet of claim 4, comprising the following components in percentage by weight:
5 to 10 percent of choline alfoscerate
14 to 62 percent of mannitol
Silicified microcrystalline cellulose 30-67%
3-5% of croscarmellose sodium
0.8 to 1.5 percent of silicon dioxide
0.2 to 1.0 percent of sucralose
0.5 to 1.5 percent of magnesium stearate.
6. The orally disintegrating tablet of claim 5, comprising the following components in percentage by weight:
5 to 10 percent of choline alfoscerate
38 to 50 percent of mannitol
Silicified microcrystalline cellulose 40-50%
3-5% of croscarmellose sodium
0.8 to 1.5 percent of silicon dioxide
0.2 percent of sucralose
0.5 to 0.7 percent of magnesium stearate.
7. The orally disintegrating tablet according to any one of claims 5, wherein the preparation process comprises the steps of:
(1) mixing prescription dose of choline alfoscerate, mannitol, silicified microcrystalline cellulose, croscarmellose sodium, silicon dioxide and sucralose;
(2) adding the magnesium stearate with the prescription amount into the mixed granules prepared in the step (1), mixing and tabletting, wherein the preferable preparation method comprises the following steps of (1) mixing the choline alfoscerate with the prescription amount with silicon dioxide, and sieving the mixture twice through a 100-200-mesh sieve, (2) adding the mannitol, silicified microcrystalline cellulose, croscarmellose sodium and sucralose with the prescription amount into the mixed granules prepared in the step (1) for mixing, (3) adding the magnesium stearate with the prescription amount into the mixed granules prepared in the step (2), mixing and tabletting; the preparation method further comprises the following steps of (1) mixing choline alfoscerate with a prescription amount with silicon dioxide, and sieving the mixture twice with a 100-200-mesh sieve, (2) adding silicified microcrystalline cellulose with the prescription amount into the granules prepared in the step (1) and mixing; (3) adding the prescription amount of mannitol, croscarmellose sodium and sucralose into the mixed granules prepared in the step (2) for mixing, and (4) adding the prescription amount of magnesium stearate into the mixed granules prepared in the step (3), mixing and tabletting.
8. The orally disintegrating tablet of claim 7, wherein said step (1) comprises mixing a prescribed amount of choline alfoscerate with silica, and sieving twice through a 120-200 mesh sieve.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910576343.5A CN112137971A (en) | 2019-06-28 | 2019-06-28 | Orally disintegrating tablet of choline alfoscerate and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910576343.5A CN112137971A (en) | 2019-06-28 | 2019-06-28 | Orally disintegrating tablet of choline alfoscerate and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112137971A true CN112137971A (en) | 2020-12-29 |
Family
ID=73869467
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910576343.5A Pending CN112137971A (en) | 2019-06-28 | 2019-06-28 | Orally disintegrating tablet of choline alfoscerate and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112137971A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113041252A (en) * | 2021-03-22 | 2021-06-29 | 上海欧睿生物科技有限公司 | Alpha-GPC formula process technology with excellent moisture absorption resistance |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007010892A1 (en) * | 2005-07-19 | 2007-01-25 | Asahi Kasei Pharma Corporation | Novel phospholipid processing agent |
| CN103919715A (en) * | 2013-01-14 | 2014-07-16 | 柏法迪斯有限公司 | Controlled Release Drug Combination Containing Choline Alfoscerate Or Salt Thereof And Method For Preparing Same |
| CN105658208A (en) * | 2013-12-17 | 2016-06-08 | 株式会社大熊制药 | Film coated tablet containing choline alfoscerate and process for preparing the same |
| CN107789328A (en) * | 2016-09-07 | 2018-03-13 | 成都康弘药业集团股份有限公司 | A kind of oral disintegrating tablet containing Doneppezil Hydrochloride and preparation method thereof |
| CN109864975A (en) * | 2017-12-04 | 2019-06-11 | 成都康弘药业集团股份有限公司 | A kind of oral disnitegration tablet of Aripiprazole and preparation method thereof |
-
2019
- 2019-06-28 CN CN201910576343.5A patent/CN112137971A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007010892A1 (en) * | 2005-07-19 | 2007-01-25 | Asahi Kasei Pharma Corporation | Novel phospholipid processing agent |
| CN103919715A (en) * | 2013-01-14 | 2014-07-16 | 柏法迪斯有限公司 | Controlled Release Drug Combination Containing Choline Alfoscerate Or Salt Thereof And Method For Preparing Same |
| CN105658208A (en) * | 2013-12-17 | 2016-06-08 | 株式会社大熊制药 | Film coated tablet containing choline alfoscerate and process for preparing the same |
| CN107789328A (en) * | 2016-09-07 | 2018-03-13 | 成都康弘药业集团股份有限公司 | A kind of oral disintegrating tablet containing Doneppezil Hydrochloride and preparation method thereof |
| CN109864975A (en) * | 2017-12-04 | 2019-06-11 | 成都康弘药业集团股份有限公司 | A kind of oral disnitegration tablet of Aripiprazole and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 刘文: "《药用高分子材料学》", 30 June 2017 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113041252A (en) * | 2021-03-22 | 2021-06-29 | 上海欧睿生物科技有限公司 | Alpha-GPC formula process technology with excellent moisture absorption resistance |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6060078A (en) | Chewable tablet and process for preparation thereof | |
| JP5886632B2 (en) | Immediate release pharmaceutical composition comprising oxycodone and naloxone | |
| JP3929618B2 (en) | Solid oral pharmaceutical composition for treatment of mouth-dissolving or chewing type rhinitis | |
| CN108272765B (en) | Pharmaceutical composition containing vardenafil hydrochloride, orally disintegrating tablet, and preparation and application thereof | |
| CN110475544B (en) | Orally disintegrating tablet comprising carbamate compound | |
| JP5656258B2 (en) | Orally disintegrating tablets containing galantamine | |
| Woodford et al. | Relative bioavailability of aspirin gum | |
| Rathod et al. | Medicated lozenges as an easy to use dosage form | |
| CN101198327B (en) | Solid compositions for treating middle-of-the-night insomnia and method therefor | |
| JP2705787B2 (en) | Easy to take bitterness improving H 改善 2Ｈ blocker solid preparation | |
| CN114469882A (en) | Dextromethorphan quinidine orally disintegrating tablet and application thereof | |
| US20190388392A1 (en) | Oral eliglustat transmucosal delivery system | |
| US20150141520A1 (en) | Stabilized pharmaceutical compositions of fingolimod and process for preparation thereof | |
| CN112137971A (en) | Orally disintegrating tablet of choline alfoscerate and preparation method thereof | |
| JP6258342B2 (en) | Medicinal lozenge based on ibuprofen sodium dihydrate | |
| JP5478170B2 (en) | Orally disintegrating tablets | |
| RU2690685C2 (en) | Pharmaceutical compositions containing alpelisib | |
| WO2012080216A1 (en) | Orally disintegrating tablet having a taste masking effect | |
| JP2007534742A (en) | Lozenge for sending out Dextromethorphan | |
| AU2012241189A1 (en) | Fast Dissolving Solid Dosage Form | |
| Maskare et al. | A Review on New Herbal Remedies for treatment of Mouth Ulcer | |
| CN106474080A (en) | A kind of Montelukast receives oral disintegrating tablet and preparation method thereof | |
| JP5226732B2 (en) | Compression molding for hypnosis | |
| Renuka et al. | Development and in-vitro evaluation of nicotine hard candy lozenges for smoking cessation | |
| RU2789054C2 (en) | Oral dosage form containing outer coating for fast release |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20201229 |