CN105997914A - Levetiracetam combined drug and preparation method thereof - Google Patents
Levetiracetam combined drug and preparation method thereof Download PDFInfo
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- CN105997914A CN105997914A CN201610570115.3A CN201610570115A CN105997914A CN 105997914 A CN105997914 A CN 105997914A CN 201610570115 A CN201610570115 A CN 201610570115A CN 105997914 A CN105997914 A CN 105997914A
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- levetiracetam
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- 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
- A61K31/40—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
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- 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
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- 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
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- 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
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Abstract
The invention relates to a levetiracetam combined drug which is composed of, by mass, 50-80 parts of levetiracetam, 10-20 parts of low-substitution hydroxypropyl cellulose, 1-3 parts of disintegrating agent, 1-3 parts of lubricant and 1-2 parts of micropowder silica gel. The disintegrating agent is a mixture of crosslinked sodium carboxymethyl cellulose and sodium carboxymethyl starch according to a mass ratio of 1:2.2-2.7, and the lubricant is a mixture of magnesium laurinol sulfate and magnesium stearate according to 1:3.1-3.7. The levetiracetam combined drug has the advantages that the disintegrating agent is the mixture of crosslinked sodium carboxymethyl cellulose and sodium carboxymethyl starch, so that the levetiracetam combined drug has good hygroscopicity and expandibility, and disintegrating of tablets can be realized quickly; the lubricant is the mixture of magnesium laurinol sulfate and magnesium stearate, so that fluidity and compressibility of a main drug are improved effectively.
Description
Technical field
The invention belongs to medical domain, particularly to a kind of levetiracetam composition of medicine and system thereof
Preparation Method.
Background technology
Levetiracetam (Levetiracetam), its chemical entitled Levetiratetam,
It is mainly used in adult and the add-on of more than 4 years old Patients with Epilepsy in Childhood partial seizures.Use clinically at present is mainly
Tablet.
Owing to levetiracetam is crystalline powder, mobility is very poor, and this preparation specification is relatively big, so conventional preparation work
Skill is wet granule compression tablet or dry granulation tabletting.In patent CN101068534A, UCB Pharma SA is to wet granulation
And two kinds of preparation technologies of dry granulation tabletting are contrasted, result acceleration (40 DEG C, 75%), after 6 months, uses wet granulation work
Tablet dissolution prepared by skill is the most slack-off, and uses the tablet of dry granulation process to change inconspicuous.But dry granulation process
Need to use the special installations such as dry granulating machine, and operating process is loaded down with trivial details, need circulation to pelletize, sieve, the granule one prepared
As harder and irregular, pitted skin phenomenon easily occurs after tabletting.
Also finding through retrieval, patent CN101068534A discloses a kind of levetiracetam tablet pharmaceutical composition, comprises
Relative to gross weight 80% to 95% weight of pharmaceutical composition as the levetiracetam of active component, 2.0 to 9.0% weight
Cross-linking sodium carboxymethyl cellulose (disintegrating agent), the colloidal silica anhydrous (fluidizer) of 0.0 to 3.0% weight, 0.5 to 6.0%
The polyethylene glycol 6000 (binding agent) of weight, and the magnesium stearate (lubricant) of 0.0 to 1.0% weight, described tablet medicine combines
Thing is to be prepared by dry granulation method, which solves and uses water as solvent wet granulation, the problem that after preserving 6 months, disintegrate is slowed down.
Because this pharmaceutical composition uses dry granulation and tabletting, to the selection of prescription and ratio will the harshest time can be only achieved good
Compressibility, the poor reproducibility of this method, there is content and release difference between each of prepared troche medical composition different batches
Bigger problem.
Therefore, research and develop that content difference between a kind of is little and the levetiracetam composition of medicine of different batches favorable reproducibility and
Preparation method is necessary.
Summary of the invention
The technical problem to be solved in the present invention is to provide that content difference between a kind of is little and a left side for different batches favorable reproducibility
Etiracetam composition of medicine, additionally provides the preparation method of this levetiracetam composition of medicine.
For solving above-mentioned technical problem, the technical scheme is that a kind of levetiracetam composition of medicine, its innovative point
It is: described composition of medicine is made up of the raw material of following masses part: levetiracetam 50-80 part, low-substituted hydroxypropyl cellulose
10-20 part, disintegrating agent 1-3 part, lubricant 1-3 part and micropowder silica gel 1-2 part；Wherein, described disintegrating agent is cross-linked carboxymethyl
Sodium cellulosate and the mixture of carboxymethyl starch sodium, and the mass ratio of cross-linking sodium carboxymethyl cellulose and carboxymethyl starch sodium is 1:
2.2-2.7；Described lubricant is the mixture that magnesium laurylsulfate and stearic acid are beautiful, and magnesium laurylsulfate and stearic acid beautiful
Mass ratio be 1:3.1-3.7.
Further, described composition of medicine is made up of the raw material of following masses part: levetiracetam 65 parts, low-substituted hydroxypropyl
Base cellulose 15 parts, disintegrating agent 2 parts, lubricant 2 parts and micropowder silica gel 1.5 parts.
The preparation method of a kind of above-mentioned levetiracetam composition of medicine, its innovative point is: described preparation method specifically walks
Rapid as follows:
(1) levetiracetam pulverizes and sieves, and sieve aperture is 0.15mm；
(2) low-substituted hydroxypropyl cellulose and disintegrating agent sieve, and sieve aperture is 0.15mm；
(3) sieve after the material that step (1) and step (2) obtain being mixed homogeneously with lubricant and micropowder silica gel, sieve aperture
For 0.8mm；
(4) material that step (3) obtains is carried out tabletting.
It is an advantage of the current invention that: the levetiracetam composition of medicine of the present invention, in prescription, disintegrating agent uses crosslinking carboxylic first
Base sodium cellulosate and the mixture of carboxymethyl starch sodium, and then there is good water absorption and dilatancy, it is thus possible to realize rapidly
The disintegrate of tablet；Meanwhile, lubricant uses magnesium laurylsulfate and the mixture of stearic acid U.S., effectively improves the flowing of principal agent
Property and compressibility, use direct powder compression, the phenomenon of pitted skin easily occur after overcoming tabletting, prepare between pharmaceutical composition sheet
Content difference is little, different batches favorable reproducibility.
Detailed description of the invention
The following examples can make professional and technical personnel that the present invention is more fully understood, but the most therefore by this
Bright it is limited among described scope of embodiments.
Embodiment 1
The preparation method of the present embodiment levetiracetam composition of medicine, this preparation method specifically comprises the following steps that
(1) being pulverized and sieved by the levetiracetam of 50 mass parts, sieve aperture is 0.15mm；
(2) by the low-substituted hydroxypropyl cellulose of 20 mass parts, the cross-linking sodium carboxymethyl cellulose of 0.94 mass parts and 2.06 matter
The carboxymethyl starch sodium of amount part sieves, and sieve aperture is 0.15mm；
(3) material step (1) and step (2) obtained and the magnesium laurylsulfate of 0.73 mass parts, 2.77 mass parts hard
Sieving after the micropowder silica gel mix homogeneously of fatty acid magnesium and 2 mass parts, sieve aperture is 0.8mm；
(4) material that step (3) obtains is carried out tabletting, prepare levetiracetam composition of medicine.
Embodiment 2
The preparation method of the present embodiment levetiracetam composition of medicine, this preparation method specifically comprises the following steps that
(1) being pulverized and sieved by the levetiracetam of 50 mass parts, sieve aperture is 0.15mm；
(2) by the low-substituted hydroxypropyl cellulose of 20 mass parts, the cross-linking sodium carboxymethyl cellulose of 0.81 mass parts and 2.19 matter
The carboxymethyl starch sodium of amount part sieves, and sieve aperture is 0.15mm；
(3) material step (1) and step (2) obtained and the magnesium laurylsulfate of 0.64 mass parts, 2.36 mass parts hard
Sieving after the micropowder silica gel mix homogeneously of fatty acid magnesium and 2 mass parts, sieve aperture is 0.8mm；
(4) material that step (3) obtains is carried out tabletting, prepare levetiracetam composition of medicine.
Embodiment 3
The preparation method of the present embodiment levetiracetam composition of medicine, this preparation method specifically comprises the following steps that
(1) being pulverized and sieved by the levetiracetam of 50 mass parts, sieve aperture is 0.15mm；
(2) by the low-substituted hydroxypropyl cellulose of 20 mass parts, the cross-linking sodium carboxymethyl cellulose of 0.86 mass parts and 2.14 matter
The carboxymethyl starch sodium of amount part sieves, and sieve aperture is 0.15mm；
(3) material step (1) and step (2) obtained and the magnesium laurylsulfate of 0.68 mass parts, 2.32 mass parts hard
Sieving after the micropowder silica gel mix homogeneously of fatty acid magnesium and 2 mass parts, sieve aperture is 0.8mm；
(4) material that step (3) obtains is carried out tabletting, prepare levetiracetam composition of medicine.
Embodiment 4
The preparation method of the present embodiment levetiracetam composition of medicine, this preparation method specifically comprises the following steps that
(1) being pulverized and sieved by the levetiracetam of 80 mass parts, sieve aperture is 0.15mm；
(2) by the low-substituted hydroxypropyl cellulose of 10 mass parts, the cross-linking sodium carboxymethyl cellulose of 0.29 mass parts and 0.71 matter
The carboxymethyl starch sodium of amount part sieves, and sieve aperture is 0.15mm；
(3) material step (1) and step (2) obtained and the magnesium laurylsulfate of 0.23 mass parts, 0.77 mass parts hard
Sieving after the micropowder silica gel mix homogeneously of fatty acid magnesium and 1 mass parts, sieve aperture is 0.8mm；
(4) material that step (3) obtains is carried out tabletting, prepare levetiracetam composition of medicine.
Embodiment 5
The preparation method of the present embodiment levetiracetam composition of medicine, this preparation method specifically comprises the following steps that
(1) being pulverized and sieved by the levetiracetam of 65 mass parts, sieve aperture is 0.15mm；
(2) by the low-substituted hydroxypropyl cellulose of 15 mass parts, the cross-linking sodium carboxymethyl cellulose of 0.57 mass parts and 1.43 matter
The carboxymethyl starch sodium of amount part sieves, and sieve aperture is 0.15mm；
(3) material step (1) and step (2) obtained and the magnesium laurylsulfate of 0.45 mass parts, 1.55 mass parts hard
Sieving after the micropowder silica gel mix homogeneously of fatty acid magnesium and 1.5 mass parts, sieve aperture is 0.8mm；
(4) material that step (3) obtains is carried out tabletting, prepare levetiracetam composition of medicine.
Table 1 is disintegrating agent and the contrast table of the mass ratio of each material in lubricant in embodiment 1-3.
Disintegrating agent and the contrast of the mass ratio of each material in lubricant in table 1 embodiment 1-3
Table 2 is the contrast table of the mass ratio of each material in embodiment 3-5.
The contrast of the mass ratio of each material in table 2 embodiment 3-5
Test: the tablet weight uniformity and hardness determination
According to the tablet to all embodiments of the method described by the Pharmacopoeia of the People's Republic of China one annex IA of version in 2010
Weight differential detects, and takes 20, each embodiment tablet, accurately weighed gross weight, the most averagely claims often after trying to achieve average tablet weight
The weight of sheet, every weight, compared with average sheet weight, more than 2, and must not must not have 1 beyond limit test of weight variation
Overrun 1 times.Detect qualified tablet again by hardness-testing device test tablet hardness.In this experiment, average tablet weight is all higher than
0.3g, limit test of weight variation is 5%.The tablet weight variation of levetiracetam composition of medicine and hardness balance are shown in Table 3:
The tablet weight variation of table 3 etiracetam composition of medicine and hardness balance
From upper result of the test, the left second that any levetiracetam crystal formation is prepared according to prescription of the present invention and method is drawn
Western smooth composition of medicine, tablet weight variation all meets regulation, and tablet hardness is 4-9, further preferred prescription such as embodiment 5,
Hardness is between 7-9.
The ultimate principle of the present invention and principal character and advantages of the present invention have more than been shown and described.The skill of the industry
The art personnel simply explanation it should be appreciated that the present invention is not restricted to the described embodiments, described in above-described embodiment and description
The principle of the present invention, without departing from the spirit and scope of the present invention, the present invention also has various changes and modifications, these
Changes and improvements both fall within scope of the claimed invention.Claimed scope by appending claims and
Its equivalent defines.
Claims (3)
1. a levetiracetam composition of medicine, it is characterised in that: described composition of medicine is made up of the raw material of following masses part: left
Etiracetam 50-80 part, low-substituted hydroxypropyl cellulose 10-20 part, disintegrating agent 1-3 part, lubricant 1-3 part and micropowder silica gel 1-
2 parts；Wherein, described disintegrating agent is the mixture of cross-linking sodium carboxymethyl cellulose and carboxymethyl starch sodium, and cross-linked carboxymethyl
The mass ratio of sodium cellulosate and carboxymethyl starch sodium is 1:2.2-2.7；Described lubricant is magnesium laurylsulfate and stearic acid
Beautiful mixture, and magnesium laurylsulfate and the beautiful mass ratio of stearic acid be 1:3.1-3.7.
Levetiracetam composition of medicine the most according to claim 1, it is characterised in that: described composition of medicine is by following masses
The raw material composition of part: levetiracetam 65 parts, low-substituted hydroxypropyl cellulose 15 parts, disintegrating agent 2 parts, lubricant 2 parts and micropowder
1.5 parts of silica gel.
3. the preparation method of a claim 1 levetiracetam composition of medicine, it is characterised in that: described preparation method specifically walks
Rapid as follows:
Levetiracetam pulverizes and sieves, and sieve aperture is 0.15mm；
Low-substituted hydroxypropyl cellulose and disintegrating agent sieve, and sieve aperture is 0.15mm；
Sieving after being mixed homogeneously with lubricant and micropowder silica gel by the material that step (1) and step (2) obtain, sieve aperture is
0.8mm；
The material that step (3) obtains is carried out tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610570115.3A CN105997914A (en) | 2016-07-20 | 2016-07-20 | Levetiracetam combined drug and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610570115.3A CN105997914A (en) | 2016-07-20 | 2016-07-20 | Levetiracetam combined drug and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105997914A true CN105997914A (en) | 2016-10-12 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610570115.3A Pending CN105997914A (en) | 2016-07-20 | 2016-07-20 | Levetiracetam combined drug and preparation method thereof |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101693017A (en) * | 2009-10-28 | 2010-04-14 | 北京赛科药业有限责任公司 | Medicament composition of levetiracetam and preparation process |
| US20110064807A1 (en) * | 2005-01-27 | 2011-03-17 | Ucb Pharma S.A. | Extended release formulation of levetiracetam |
| CN102973531A (en) * | 2012-12-18 | 2013-03-20 | 天津南开允公医药科技有限公司 | Levetiracetam medicine composition and preparation method thereof |
| CN104666263A (en) * | 2015-02-09 | 2015-06-03 | 海南华益泰康药业有限公司 | Tablet containing levetiracetam and preparation method of tablet |
-
2016
- 2016-07-20 CN CN201610570115.3A patent/CN105997914A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110064807A1 (en) * | 2005-01-27 | 2011-03-17 | Ucb Pharma S.A. | Extended release formulation of levetiracetam |
| CN101693017A (en) * | 2009-10-28 | 2010-04-14 | 北京赛科药业有限责任公司 | Medicament composition of levetiracetam and preparation process |
| CN102973531A (en) * | 2012-12-18 | 2013-03-20 | 天津南开允公医药科技有限公司 | Levetiracetam medicine composition and preparation method thereof |
| CN104666263A (en) * | 2015-02-09 | 2015-06-03 | 海南华益泰康药业有限公司 | Tablet containing levetiracetam and preparation method of tablet |
Non-Patent Citations (3)
| Title |
|---|
| 刘平等: "左乙拉西坦片的制备及处方优化", 《中国医院药学杂志》 * |
| 叶勇主编: "《制药工艺学》", 31 January 2014, 华南理工大学出版社 * |
| 闫丽霞主编: "《中药制剂技术》", 31 August 2004, 化学工业出版社 * |
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Application publication date: 20161012 |
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