CN115350178A - Pharmaceutical composition containing levetiracetam - Google Patents

Pharmaceutical composition containing levetiracetam Download PDF

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CN115350178A
CN115350178A CN202211016251.XA CN202211016251A CN115350178A CN 115350178 A CN115350178 A CN 115350178A CN 202211016251 A CN202211016251 A CN 202211016251A CN 115350178 A CN115350178 A CN 115350178A
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binder
levetiracetam
pharmaceutical composition
dextrin
weight
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CN115350178B (en
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宋立华
朱双鹏
宋森
吴成玲
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Zhejiang Jingxin Pharmaceutical Co Ltd
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Zhejiang Jingxin Pharmaceutical Co Ltd
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    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • 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
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • 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
    • 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
    • A61K9/2063—Proteins, e.g. gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/282—Organic compounds, e.g. fats
    • 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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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Medicinal Chemistry (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention provides a pharmaceutical composition containing levetiracetam, which comprises the following components in part by weight: 70-90% of levetiracetam, 6-10% of disintegrant, 1-5% of first binder, 1-3% of second binder, 1-10% of filler and 0.1-2% of lubricant, wherein the first binder comprises one or more of povidone, polyethylene glycol, gelatin and cellulose derivative, and the second binder is dextrin. According to the levetiracetam-containing pharmaceutical composition, the dextrin and other binders are used to form the binder combination, and the dextrin and other binders are adjusted to a certain dosage ratio, so that the levetiracetam-containing pharmaceutical composition has the advantages of rapid disintegration, rapid drug release, no obvious change in dissolution rate after long-term storage, high stability and the like.

Description

Pharmaceutical composition containing levetiracetam
Technical Field
The invention relates to a pharmaceutical composition, and in particular relates to a pharmaceutical composition containing levetiracetam.
Background
Levetiracetam is a novel antiepileptic drug developed by UCB company of Belgium and has the chemical name of (S) -2- (2-oxo-1-pyrrolidine) butanamide. The medicine has remarkable antiepileptic effect, and has excellent tolerance and safety.
Levetiracetam tablets from UCB were marketed in the united states in 1999 for the treatment of partial seizures in adults and children over 4 years of age in epileptic patients. To improve treatment efficacy, reduce the incidence of adverse events, and improve patient compliance, the UCB company continues to develop extended release formulations of levetiracetam, marketed in the united states in 2008, for treatment of patients with partial seizures aged 16 years and older.
Chinese patent CN112870176B provides a levetiracetam tablet and a preparation method thereof, the levetiracetam tablet comprises levetiracetam, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide and magnesium stearate, and dry granulation is adopted in the process of preparing the levetiracetam tablet.
Some pharmaceutical compositions containing levetiracetam disclosed in the prior art have the problems of slow drug release speed, obvious dissolution change after long-term storage and the like.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides the levetiracetam medicine which is rapidly disintegrated, rapidly released, free from obvious change of dissolution rate in long-term storage and high in stability.
The invention provides a pharmaceutical composition containing levetiracetam, which comprises the following components in part by weight: 70-90% of levetiracetam, 6-10% of disintegrant, 1-5% of first binder, 1-3% of second binder, 1-10% of filler and 0.1-2% of lubricant, wherein the first binder comprises one or more of povidone, polyethylene glycol, gelatin and cellulose derivative, and the second binder is dextrin.
In some embodiments, the dextrin comprises one or more of white dextrin, yellow dextrin, maltodextrin.
In some embodiments, the dextrin is preferably white dextrin.
In some embodiments, the first binder is povidone. The polyvidone can be polyvidone K30, polyvidone K25, polyvidone K17, etc.
In some embodiments, the first binder is povidone K30.
In some embodiments, the weight ratio of the first binder to the second binder is 2. For example, the weight ratio of the first binder to the second binder is 4.
In some embodiments, the weight ratio of the first binder to the second binder is 1.5. For example, the weight ratio of the first binder to the second binder is 4.
In some embodiments, the weight ratio of the sum of the weight of the first binder and the second binder to the weight of levetiracetam is 1. For example, the sum of the weights of the first binder and the second binder is m1, the weight of levetiracetam is m2, m1: m2 is 1.
In some embodiments, the weight ratio of the sum of the weight of the first binder and the second binder to the weight of levetiracetam is 1. For example, the sum of the weights of the first binder and the second binder is m1, the weight of levetiracetam is m2, m1: m2 is 1.
In some embodiments, the disintegrant comprises one or more of croscarmellose sodium, sodium carboxymethyl starch, low substituted hydroxypropyl cellulose, crospovidone. For example, the disintegrant is croscarmellose sodium. As another example, disintegrants include croscarmellose sodium and sodium starch glycolate.
In some embodiments, the filler comprises one or more of microcrystalline cellulose, lactose, starch. For example, the filler is microcrystalline cellulose. As another example, the filler is lactose.
In some embodiments, the lubricant comprises one or more of magnesium stearate, aerosil, talc, polyethylene glycol, magnesium lauryl sulfate, sodium lauryl sulfate. For example, the lubricant is magnesium stearate. As another example, the lubricant is polyethylene glycol.
In some embodiments, the pharmaceutical composition further comprises a coating material, wherein the weight of the coating material is 1-5% of the total weight of the plain tablet, and the total weight of the plain tablet is the sum of the weights of the levetiracetam, the disintegrant, the first binder, the second binder, the filler and the lubricant. For example, the weight of the coating material can be 1%, 2%, 2.5%, 3%, 3.5%, 4%, or 5% of the total weight of the tablet, and the like.
The invention also provides a method for preparing the levetiracetam tablet, wherein the levetiracetam, the disintegrating agent, the first adhesive, the second adhesive, the filling agent and the lubricating agent form a tablet core, and the coating material is formed on the surface of the tablet core to form a coating layer.
Coating materials suitable for use in the present invention are various, for example, opadry, gastric film coating premixes (model 85F18422, model 85F640021, model 85F110022, model 85F 20694) available from the carrekan manufacturer, and the like.
The invention has the following beneficial effects: according to the levetiracetam-containing pharmaceutical composition, the dextrin and other binders are used to form the binder combination, and the dextrin and other binders are adjusted to a certain dosage ratio, so that the levetiracetam-containing pharmaceutical composition has the advantages of rapid disintegration, rapid drug release, no obvious change in dissolution rate after long-term storage, high stability and the like.
According to the invention, the types and the dosages of the adhesive and other components are adjusted, so that the use of a glidant is omitted, and the influence of the glidant on the stability of the pharmaceutical composition is avoided.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
Example 1 levetiracetam tablets
Figure BDA0003812631200000031
The preparation method comprises the following steps:
1. and (4) pretreating raw materials and auxiliary materials.
And (3) sieving the levetiracetam with a 20-mesh sieve, and sieving the croscarmellose sodium with a 40-mesh sieve for later use.
2. And (4) granulating in one step by using a fluidized bed.
Slurry preparation: weighing povidone K30 and dextrin according to the prescription amount, adding a proper amount of purified water, and uniformly stirring to obtain the mixed slurry. The weight of the syrup was M1 and the sum of the weight of levetiracetam and croscarmellose sodium used in the fluid bed one-step granulation process was M2, M1= M2 × 40%.
One-step granulation by a fluidized bed: weighing levetiracetam and croscarmellose sodium according to the prescription, mixing the levetiracetam and the croscarmellose sodium, putting the mixed levetiracetam and croscarmellose sodium into a fluidized bed for preheating, setting the air inlet temperature to be 60-80 ℃ and the fan flow to be 80-100m 3 And h, starting heating, controlling the actual material temperature not to exceed 50 ℃, starting top spraying liquid after the material temperature reaches at least 30 ℃, controlling the liquid supply rotation speed to be 5-12rpm, and controlling the atomization pressure to be 0.2-0.3bar. After spraying, a rapid moisture tester is adopted to detect the loss on drying (65 ℃,5 min), drying is stopped until the Loss On Drying (LOD) of dry particles is less than 1.0 percent, and parameters are recorded every 10 min.
3. And (5) finishing the granules.
After drying, the granules are sieved by a 40-mesh sieve, and the granules above the 40-mesh sieve are manually granulated.
4. And (4) mixing.
Adding magnesium stearate and another part of croscarmellose sodium into the granules obtained after finishing, and mixing in a mixer for 5min to obtain a mixture.
5. And (5) tabletting.
And (4) tabletting the mixture obtained in the step (4) to obtain plain tablets.
6. And (4) coating.
Dispersing the coating premix in purified water to obtain a coating solution with a solid content of 18-20%, and coating the plain tablets by using the coating solution, wherein the coating temperature is controlled at 40 +/-5 ℃, and after the coating is finished, the weight of the plain tablets is increased by 3.0%.
The coating premix was a gastric-soluble film coating premix model 85F18422 from Carlekang, inc.
Example 2 levetiracetam tablets
Figure BDA0003812631200000041
Figure BDA0003812631200000051
In example 2, levetiracetam tablets were prepared using the method described in example 1.
Example 3 levetiracetam tablets
Figure BDA0003812631200000052
In example 3, levetiracetam tablets were prepared using the method described in example 1.
Example 4 levetiracetam tablets
Figure BDA0003812631200000053
In example 4, levetiracetam tablets were prepared using the method described in example 1.
Example 5 levetiracetam tablets
Figure BDA0003812631200000061
In example 5, levetiracetam tablets were prepared using the method described in example 1.
Example 6 levetiracetam tablets
Figure BDA0003812631200000062
In example 6, levetiracetam tablets were prepared using the method described in example 1.
Example 7
Dissolution tests were performed on levetiracetam tablets prepared according to the formulation ratios and preparation methods of examples 1-6, using dissolution media: 900mL of water, temperature: 37 ℃, revolution: 50rpm.
The detected cumulative dissolution rates (%) of the levetiracetam tablet at 5min, 10min, 15min, 30min and 45min are as follows:
sampling time (min) Example 1 Example 2 Example 3 Example 4 Example 5 Example 6
5 49％ 39％ 43％ 33％ 45％ 35％
10 85％ 75％ 79％ 61％ 81％ 72％
15 96％ 87％ 91％ 75％ 93％ 79％
30 99％ 90％ 94％ 79％ 96％ 84％
45 100％ 91％ 96％ 80％ 95％ 84％
Example 8
Packaging the levetiracetam tablets prepared according to the prescription proportion and the preparation method in the example 1 by adopting a conventional tablet packaging material, placing the packaged tablets in an environment with the temperature of 25 +/-2 ℃ and the relative humidity of 60 +/-5%, storing for 18 months, taking out, and carrying out an in-vitro dissolution test, wherein the test conditions and the method are the same as those in the example 7. The cumulative dissolution rates of the levetiracetam tablet stored for 18 months at 5min, 10min, 15min, 30min and 45min are respectively 48%, 83%, 95%, 98% and 99%.
The levetiracetam tablets prepared according to the prescription proportion and the preparation method in the example 6 are packaged by adopting a conventional tablet packaging material, the packaged tablets are placed in an environment with the temperature of 25 +/-2 ℃ and the relative humidity of 60 +/-5 percent, are stored for 18 months and then are taken out for in-vitro dissolution test, and the test conditions and the method are the same as those in the example 7. The cumulative dissolution rates of levetiracetam tablets stored for 18 months at 5min, 10min, 15min, 30min and 45min are respectively 30%, 63%, 68%, 72% and 73%.
The dissolution rate of the levetiracetam tablet prepared according to the prescription proportion and the preparation method in the embodiment 1 after being stored for 18 months does not obviously change from the dissolution rate just prepared, while the dissolution rate of the levetiracetam tablet prepared according to the prescription proportion and the preparation method in the embodiment 6 after being stored for 18 months obviously changes from the dissolution rate just prepared, and the dissolution rate after being stored for 18 months obviously decreases. This demonstrates that the levetiracetam tablets of example 1 disintegrate rapidly, release the drug rapidly, and remain relatively stable in dissolution during long-term storage without significant degradation.

Claims (10)

1. A pharmaceutical composition comprising levetiracetam, wherein the pharmaceutical composition comprises: 70-90% of levetiracetam, 6-10% of disintegrant, 1-5% of first binder, 1-3% of second binder, 1-10% of filler and 0.1-2% of lubricant, wherein the first binder comprises one or more of povidone, polyethylene glycol, gelatin and cellulose derivative, and the second binder is dextrin.
2. The pharmaceutical composition of claim 1, wherein the dextrin comprises one or more of white dextrin, yellow dextrin, and maltodextrin.
3. The pharmaceutical composition of claim 2, wherein the dextrin is a white dextrin.
4. The pharmaceutical composition of claim 1, wherein the first binder is povidone.
5. The pharmaceutical composition according to claim 1, wherein the weight ratio of the first binder to the second binder is from 2 to 1.
6. The pharmaceutical composition according to claim 1, wherein the weight ratio of the sum of the weights of the first and second binders to the levetiracetam is 1.
7. The pharmaceutical composition according to claim 1, wherein the disintegrant comprises one or more of croscarmellose sodium, sodium carboxymethyl starch, low substituted hydroxypropyl cellulose, crospovidone.
8. The pharmaceutical composition of claim 1, wherein the filler comprises one or more of microcrystalline cellulose, lactose, and starch.
9. The pharmaceutical composition of claim 1, wherein the lubricant comprises one or more of magnesium stearate, aerosil, talc, polyethylene glycol, magnesium lauryl sulfate, and sodium lauryl sulfate.
10. The pharmaceutical composition of claim 1, further comprising a coating material, wherein the weight of the coating material is 1-5% of the total weight of the plain tablet, and the total weight of the plain tablet is the sum of the weights of the levetiracetam, the disintegrant, the first binder, the second binder, the filler, and the lubricant.
CN202211016251.XA 2022-08-24 2022-08-24 Pharmaceutical composition containing levetiracetam Active CN115350178B (en)

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Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050013857A1 (en) * 2003-05-07 2005-01-20 Yourong Fu Highly plastic granules for making fast melting tablets
US20090074854A1 (en) * 2005-03-30 2009-03-19 Genpharm Inc. Combined-step process for pharmaceutical compositions
CN101584673A (en) * 2009-07-13 2009-11-25 浙江京新药业股份有限公司 Levetiracetam tablet and preparation method
CN102068414A (en) * 2009-11-23 2011-05-25 湖州来色生物基因工程有限公司 Levetiracetam sustained-release tablets and preparation method thereof
WO2011136751A2 (en) * 2010-04-26 2011-11-03 Mahmut Bilgic Water soluble pharmaceutical composition
CN102716097A (en) * 2012-05-29 2012-10-10 浙江华海药业股份有限公司 Method for controlling medicament release rate of orally disintegrating tablet
JP2021028326A (en) * 2019-08-09 2021-02-25 日本ジェネリック株式会社 Tablet comprising levetiracetam
JP2021098671A (en) * 2019-12-23 2021-07-01 ダイト株式会社 Pharmaceutical composition containing levetiracetam

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050013857A1 (en) * 2003-05-07 2005-01-20 Yourong Fu Highly plastic granules for making fast melting tablets
US20090074854A1 (en) * 2005-03-30 2009-03-19 Genpharm Inc. Combined-step process for pharmaceutical compositions
CN101584673A (en) * 2009-07-13 2009-11-25 浙江京新药业股份有限公司 Levetiracetam tablet and preparation method
CN102068414A (en) * 2009-11-23 2011-05-25 湖州来色生物基因工程有限公司 Levetiracetam sustained-release tablets and preparation method thereof
WO2011136751A2 (en) * 2010-04-26 2011-11-03 Mahmut Bilgic Water soluble pharmaceutical composition
CN102716097A (en) * 2012-05-29 2012-10-10 浙江华海药业股份有限公司 Method for controlling medicament release rate of orally disintegrating tablet
JP2021028326A (en) * 2019-08-09 2021-02-25 日本ジェネリック株式会社 Tablet comprising levetiracetam
JP2021098671A (en) * 2019-12-23 2021-07-01 ダイト株式会社 Pharmaceutical composition containing levetiracetam

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