CN107519141A - A kind of Lamotrigine microplate and preparation method thereof - Google Patents
A kind of Lamotrigine microplate and preparation method thereof Download PDFInfo
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- CN107519141A CN107519141A CN201610454283.6A CN201610454283A CN107519141A CN 107519141 A CN107519141 A CN 107519141A CN 201610454283 A CN201610454283 A CN 201610454283A CN 107519141 A CN107519141 A CN 107519141A
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- microplate
- lamotrigine
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- raw material
- granulation
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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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
-
- 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
- A61K9/2004—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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of Lamotrigine microplate preparation, a kind of and method for preparing Lamotrigine microplate, with Lamotrigine, adhesive, the raw materials such as filler, pass through the preparation methods such as top spray fluidized bed granulation, the good Lamotrigine microplate of compressibility has been prepared, the Lamotrigine microplate of the present invention can be with low dose of multiple dosing, especially for the big crowd of individual Difference of Metabolism, such as the elderly and child, it can count and take, accomplish precisely to be administered, and the crowd being had any problem for taking conventional formulation, the compliance of medication can be improved, and the method that the present invention uses is simple, raw material is easily obtained, it is easy to industrialized production.
Description
Technical field
The invention belongs to technical field of medicine, and in particular to a kind of Lamotrigine microplate, and provide a kind of
Method for preparing Lamotrigine microplate.
Background technology
Epileptics is a kind of chronic recurrent nervous system common disease as caused by Different types of etiopathogenises, with cranial nerve
First paradoxical discharge causes repeatedly epilepsy outbreak to be characterized, and illness rate 5%, China there are about epileptic 900 at present
Ten thousand, annual new cases about 400,000.Lamotrigine, chemical name 3,5- diaminourea -6- (2,3- dichlorophenyl)
- 1,2,4- triazines, it is a kind of antiepileptic of phenyl triazines.Lamotrigine mainly acts on voltage-dependent
Sodium channel, there is inhibitory action to discharging repeatedly, it is also possible to act on glutamic acid related neurotransmitters.Paddy can be suppressed
The antiepileptic of propylhomoserin and aspartic acid, presynaptic membrane can be stablized, suppress the release of glutamic acid and aspartic acid.
It is mainly used in treating intractable epilepsy.The conventional Lamotrigine piece of Chinese market is ordinary tablet at present, containing 25mg,
The tablet formulation of 50mg, 100mg, 150mg active component has been approved by being used to sell.
Microplate refers to the micro tablet between 1~3mm through the diameter that special tablet press machine stamping compacting forms, micro-
Piece belongs to dosage dispersiveness preparation, dispersed in intestines and stomach after the oral microplate of patient, reduces to intestines and stomach
Excitant, the stomach transhipment of medicine and absorbs that to be influenceed smaller thus individual difference by gastric emptying rate small；It is micro-
The drug release behavior of piece is the summation for the multiple junior unit drug release behaviors for forming a dosage, oral rear indivedual junior units
The defects of preparation technology will not produce serious influence to the drug release behavior of overall preparation.For drug metabolism
The big crowd of body otherness, such as the elderly and child, or for the medicine that dosage need to adjust at any time, it is micro-
Piece is a kind of more satisfactory form of administration, and patient can carry out counting clothes according to personalized medicine scheme to microplate
With metering is more accurate.Compared with other multiple-unit formulations, microplate shape is more regular, and size is more uniform.
Because microplate is formed through fixed mould compacting, thus possesses the feature of conventional tablet, its piece weight and size are all
Controllable precise, the favorable reproducibility of production, each the equal sized of microplate unit, weight are identical, medicament contg phase
Together.
Lamotrigine oral formulations are mainly tablet in the market, and are entirely the dosage specification for adult,
But in clinical practice, Lamotrigine generally needs effect to carry out dosage adjustment.When Lamotrigine is used for small childhood,
Its dosage needs to be calculated according to the kg body weight of children, and existing Lamotrigine formulation can not meet that personalized medicine will
Ask, it is impossible to convenient and divided dose exactly, can not accomplish precisely to be administered.In addition, when existing pharmaceutical dosage form is taken,
Because formulation volume is excessive, for children, old man and the inconvenient patient of tablet, the compliance of medication are swallowed
It is poor.
The content of the invention
To overcome prior art defect, the present invention provides a kind of Lamotrigine microplate preparation.Pass through special granulation
Formula and preparation technology, Lamotrigine microplate of the invention can be with low dose of accurate administrations, especially for individual
The big crowd of body Difference of Metabolism, such as the elderly and child, it can accomplish precisely to be administered, so that it is guaranteed that medicine is treated
While effect, reduce because dosage is inaccurate and may caused by adverse reaction generation.And for taking conventional system
The crowd that agent is had any problem, microplate are easy to swallow, and can improve the compliance of medication.
For achieving the above object, the invention provides a kind of Lamotrigine microplate preparation, its prescription raw material and
Its amount ratio is as follows：
Lamotrigine microplate preparation of the present invention, wherein raw material and its amount ratio are preferably as follows in the microplate：
Another optimizing prescriptions raw material of Lamotrigine microplate preparation and its amount ratio of the present invention are as follows：
Wherein described filler in starch, pregelatinized starch, dextrin, microcrystalline cellulose, lactose one
Kind is a variety of.Described adhesive is selected from：HPMC, PVP, gelatin, poloxamer, microcrystalline cellulose,
One or more in polyvinylpyrrolidone.The lubricant is selected from：Magnesium stearate, talcum powder, corn form sediment
One or more in powder, stearic acid, calcium stearate, talcum, behenic acid calcium.The disintegrant is selected from：Hand over
Join in PVP, sodium carboxymethyl starch, Ac-Di-Sol, gas-producing disintegrant, sodium alginate etc.
It is one or more.
The auxiliary material that microplate preparation of the present invention includes is not limited to the species enumerated in the content of the invention and embodiment,
Other medicines auxiliary material can also be included, on condition that not influenceing the compressing of microplate.Such as surface can also be included
Activating agent, the surfactant are chosen as：D-sorbite, mannitol, lauryl sodium sulfate, fat
Alcohol APEO, APES etc..
The spatial form of microplate can select as needed in principle.Microplate in the present invention preferably in cylinder,
Oval or spherical spatial form.Preferably height and diameter can be 1~4mm cylinder, highly
Can arbitrarily be selected as needed with diameter, such as height and diameter can be respectively 1.5mm, 2mm, 2.5mm,
3mm, 3.5mm, 4mm etc..
In the microplate preparation of the present invention, the surface of microplate can also carry out coating cladding with known method.Such as
By coating at least one layer of coating active material Lamotrigine can be made to control and (generally delay) in aqueous medium
Release.Suitable controllable release coating contains wax or polymer not soluble in water, preferred, ethyl.
In addition to polymer not soluble in water, the release rate of active material preferably can also be reached by using quantity
The material of a 30wt..% non-control release arbitrarily adjusts, preferably water miscible polymer such as polyvinyl pyrrole
Alkanone or water miscible cellulose, preferably hydroxypropyl methyl cellulose or hydroxypropyl cellulose, and/or known
Plasticizer.
In addition to controllable release coating, micro-tablet of the invention can also have other coating.Therefore, may be used
To use a kind of coating containing active material, after oral administration, active material can be with non-control from this coating
The mode of system discharges.
In addition to controllable coatings, the coating that microplate preparation of the invention can also contain for example can be with a kind of pH
The mode of dependence dissolves, it is ensured that microplate preparation does not dissolve by stomach, is just discharged until reaching enteron aisle.
Described Lamotrigine microplate preparation can also be loaded capsule by the present invention, be prepared as the oral system of capsule form
Agent, the micro-tablet of the controllable release medicine containing certain amount, the number of micro-tablet are released according to single in capsule
Time and the medication amount that will complete to discharge are put to determine.In capsule the number of micro-tablet be preferably enough to daily to
The dosage of medicine once or twice.It is with the advantages of this dosage form：The dosage of active component can directly be counted many
Segmented between several micro-tablets, but due to dosage in capsule it has been determined that therefore patient need not be cumbersome again
Count.
Microplate preparation of the present invention can be used alone, can also be with special doser such as medicine point
It is used cooperatively together with device, to provide more convenient accurately administration.
It is a further object to provide a kind of preparation method of Lamotrigine microplate, the microplate can use
The granulation of fluid bed top spray, wet granulation, dry granulation or fluid bed bottom spray method of granulating are prepared.
Such as when using top spray granulating process, preparation method is as follows：Lamotrigine, adhesive are added to pure
Change in water, stirring to formation clear transparent solutions is as granulation binders solution for standby；By filler by premixing
Afterwards, it is put into fluid bed top spray pot；Fluid bed air blast is opened, adjusts atomizing pressure and air quantity EAT,
Binder solution is sprayed into simultaneously carries out top spray granulation；After agent solution to be bonded sprays into, particle is taken out, entered
The dry whole grain of row；After the dry particl of gained is uniformly mixed with the lubricant of recipe quantity, mixed material is shifted paramount
Tabletting is carried out on fast rotary pelleting machine, gets product tablet.
Or during using wet granulation technology, preparation method is：Lamotrigine, filler and adhesive are put in
In wet granulator pot, after mixing, spray into purified water and carry out wet granulation, wet whole grain, be subsequently dried,
Particle is through overdrying whole grain after drying；After dry particl is uniformly mixed with recipe quantity lubricant, mixed material is shifted
Tabletting is carried out on to high speed rotary tablet press, both obtains finished tablet.
During using dry granulation process, preparation method is：By main ingredient Lamotrigine and other in addition to lubricant
After auxiliary material is well mixed, mixed material is added in dry granulating machine, obtains suitable dry method pelleting；Particle
After uniformly being mixed with lubricant, mixed material is transferred on high speed rotary tablet press and carries out tabletting, both obtain finished product
Tablet.
Embodiment
Embodiment 1：
| Title | Dosage |
| Lamotrigine | 2mg |
| Microcrystalline cellulose 102 | 9.46mg |
| Lactose Flawlac100 | 9.44mg |
| Sodium carboxymethyl starch | 0.66mg |
| Magnesium stearate | 0.44mg |
Preparation technology is as follows：Weigh Lamotrigine, microcrystalline cellulose 102, lactose Flawlac100 and carboxylic first
Base sodium starch uniformly mixes, and then adds magnesium stearate and mixes 2~5min, mixed material is transferred at a high speed
Rotary pelleting machine carries out tabletting, both obtains finished product Lamotrigine micro-tablet.
Embodiment 2：
| Title | Dosage |
| Lamotrigine | 2mg |
| MCC | 9.22mg |
| Lactose granulac200 | 20mg |
| Sodium carboxymethyl starch | 0.66mg |
| PVP K30 | 0.66mg |
| Magnesium stearate | 0.44mg |
Preparation technology is as follows：PVP K30 is configured to 3%~8% solution, Lamotrigine, lactose
Granulac200 and sodium carboxymethyl starch are put in wet granulator pot, after mixing, open blade
PVP K30 solution is sprayed into simultaneously and carries out wet granulation, whole grain, is subsequently placed into fluid bed and is dried,
Particle is through overdrying whole grain after drying；After dry particl is uniformly mixed with recipe quantity magnesium stearate, mixed material is turned
Move to and tabletting is carried out on high speed rotary tablet press, both obtain finished product Lamotrigine micro-tablet.
Embodiment 3：
| Title | Dosage |
| Lamotrigine | 3mg |
| MCC | 20.5mg |
| PVPP | 1mg |
| Magnesium stearate | 0.8mg |
Preparation technology：, will be mixed after Lamotrigine, MCC and PVPP are well mixed
Compound material is added in dry granulating machine, obtains suitable dry method pelleting；After particle uniformly mixes with magnesium stearate,
Mixed material is transferred on high speed rotary tablet press and carries out tabletting, both obtains finished tablet.
Embodiment 4
Preparation technology：Lamotrigine, PVP K30 are added in purified water, stirring to formation clear
Solution is as granulation binders solution for standby；By microcrystalline cellulose 102, cross-linked carboxymethyl cellulose is received by pre-
After mixed, it is put into fluid bed top spray pot；Fluid bed air blast is opened, atomizing pressure is adjusted and air quantity enters wind-warm syndrome
Degree, while spray into binder solution and carry out top spray granulation；After agent solution to be bonded sprays into, particle is taken out,
Carry out dry whole grain；After the dry particl of gained is uniformly mixed with the magnesium stearate of recipe quantity, mixed material is shifted
Tabletting is carried out on to high speed rotary tablet press, both obtains finished product microplate preparation.
Claims (10)
1. a kind of Lamotrigine microplate, it is characterised in that raw material and its amount ratio are as follows in the microplate：
2. microplate according to claim 1, it is characterised in that in the microplate under raw material and its amount ratio：
3. microplate according to claim 1, it is characterised in that in the microplate under raw material and its amount ratio：
4. according to the microplate described in any one of claims 1 to 3, wherein described filler is selected from starch, pregelatinated
One or more in starch, dextrin, microcrystalline cellulose, lactose.
5. according to the microplate described in any one of Claims 1 to 4, wherein described adhesive is selected from：HPMC, gather
The one or more in ketone, gelatin, poloxamer, microcrystalline cellulose, polyvinylpyrrolidone are tieed up, it is excellent
Select PVP.
6. according to the microplate described in any one of Claims 1 to 5, wherein the lubricant is selected from：Magnesium stearate, cunning
One or more in stone flour, cornstarch, stearic acid, calcium stearate, talcum, behenic acid calcium, it is excellent
Elect magnesium stearate as.
7. according to the microplate described in any one of claim 1~6, wherein the microplate is in cylinder, ellipse or ball
The spatial form of shape, microplate is preferably in 1~3mm of height, a diameter of 1~3mm cylinder.
8. it is also wrapped on one or more layers feature outside the microplate described in any one of claim 1~7, wherein microplate
Coatings.
9. the preparation method of any one of the claim 1~8 Lamotrigine microplate, it is characterised in that the microplate is adopted
With the granulation of fluid bed top spray, wet granulation, dry granulation, direct powder compression or fluid bed bottom spray grain
Method is prepared.
A kind of 10. capsule, it is characterised in that the Rameau three containing any one of claim 1~8 in the capsule
Piperazine microplate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610454283.6A CN107519141A (en) | 2016-06-21 | 2016-06-21 | A kind of Lamotrigine microplate and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610454283.6A CN107519141A (en) | 2016-06-21 | 2016-06-21 | A kind of Lamotrigine microplate and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107519141A true CN107519141A (en) | 2017-12-29 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610454283.6A Pending CN107519141A (en) | 2016-06-21 | 2016-06-21 | A kind of Lamotrigine microplate and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113456603A (en) * | 2021-07-02 | 2021-10-01 | 安徽省先锋制药有限公司 | Preparation method of lamotrigine dispersible tablets |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009063484A2 (en) * | 2007-08-03 | 2009-05-22 | Alkem Laboratories Ltd | Stable pharmaceutical composition of lamotrigine |
| US20090196924A1 (en) * | 2008-02-04 | 2009-08-06 | Pramod Kharwade | Controlled-release lamotrigine formulations |
| CN104473895A (en) * | 2014-11-20 | 2015-04-01 | 美吉斯制药（厦门）有限公司 | Lamotrigine orally disintegrating sustained release tablets |
| CN104688707A (en) * | 2015-03-24 | 2015-06-10 | 北京世桥生物制药有限公司 | Lamotrigine sustained-release tablet and preparation method thereof |
-
2016
- 2016-06-21 CN CN201610454283.6A patent/CN107519141A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009063484A2 (en) * | 2007-08-03 | 2009-05-22 | Alkem Laboratories Ltd | Stable pharmaceutical composition of lamotrigine |
| US20090196924A1 (en) * | 2008-02-04 | 2009-08-06 | Pramod Kharwade | Controlled-release lamotrigine formulations |
| CN104473895A (en) * | 2014-11-20 | 2015-04-01 | 美吉斯制药（厦门）有限公司 | Lamotrigine orally disintegrating sustained release tablets |
| CN104688707A (en) * | 2015-03-24 | 2015-06-10 | 北京世桥生物制药有限公司 | Lamotrigine sustained-release tablet and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 梅兴国主编: "《微载体药物递送系统》", 30 November 2009, 华中科技大学出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113456603A (en) * | 2021-07-02 | 2021-10-01 | 安徽省先锋制药有限公司 | Preparation method of lamotrigine dispersible tablets |
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