CN106491539B - A kind of Lamotrigine dry suspensoid agent and preparation method thereof - Google Patents
A kind of Lamotrigine dry suspensoid agent and preparation method thereof Download PDFInfo
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- CN106491539B CN106491539B CN201611175342.2A CN201611175342A CN106491539B CN 106491539 B CN106491539 B CN 106491539B CN 201611175342 A CN201611175342 A CN 201611175342A CN 106491539 B CN106491539 B CN 106491539B
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
Abstract
The invention discloses a kind of Lamotrigine dry suspensoid agents, are made of Lamotrigine and other pharmaceutical grade auxiliary materials, the pharmaceutic adjuvant includes filler, suspending agent, buffer, sweetener, flavouring agent and glidant；The dry suspensoid agent not only has the advantages that liquid suspension, i.e. improvement drug mouthfeel, and drug administration is simple, increases dosage stability；The chemically and physically stability that preparation can also be improved, improves the quality of Lamotrigine dry suspensoid agent.
Description
Technical field
Present invention relates particularly to a kind of Lamotrigine dry suspensoid agents and preparation method thereof, belong to medicine preparation field.
Background technique
Trade name of the Lamotrigine drug in the U.S. is Lamictal, is the product of GlaxoSmithKline PLC company.Primary treatment
Children and adult epileptic condition.
Currently, United States Food and Drag Administration have approved the Lamictal listing of three kinds of different dosage forms, respectively commonly
Piece, chewable tablets and oral disnitegration tablet.There is no Lamotrigine liquid preparation in the market, therefore hospital generally requires to crush when in use
Lamotrigine tablet configures liquid reagent, and the patient of convenient for children patient and dysphagia takes.
Lamotrigine is insoluble in water, and when smashed Lamotrigine tablet is added to the water, drug meeting rapid subsidence is simultaneously
And be not easy to scatter, it may thus influence the accuracy of dosage.
Chinese patent CN201510288845.X and CN201510350210.8 disclose the place of Lamotrigine oral solvent
Side and preparation method, but said preparation concentration is lower (being less than 2mg/ml), is unable to satisfy clinical demand；If you need to the prescription of high concentration,
It then needs that organic solvent is added, is unfavorable for children taking.
In addition liquid preparation is also undesirable, and applicant stored when preparing Lamotrigine liquid suspension (10mg/ml)
Square crystal generation is had in journey, the crystal of generation is difficult to separate, the situation of solution muddiness occurs, influence dosage
Accuracy.In addition when carrying out the detection of Lamotrigine liquid suspension accelerated test, Lamotrigine liquid suspension exists applicant
The impurity of overrun can be generated in 2 year validity period.
Therefore current formulations of lamotrigine, there are patient dosages to be not easy accurately, and the physics of liquid suspension and change
Learn the problems such as property stability is bad.
Summary of the invention
In order to solve above-mentioned technical problem, the present invention provides a kind of Lamotrigine dry suspensoid agent, the Lamotrigine is dry
Suspension is made of medicinal active ingredient and pharmaceutical grade auxiliary material, and the medicinal active ingredient is Lamotrigine 30-200 parts by weight；
The pharmaceutical grade auxiliary material by the filler of 10-1000 parts by weight, the suspending agent of 10-100 parts by weight, 10-100 parts by weight buffering
Agent, the sweetener of 5-50 parts by weight, the flavouring agent of 1-20 parts by weight and 1-10 parts by weight glidant composition.
Preferably, invention further provides a kind of Lamotrigine dry suspensoid agent, the Lamotrigine dry suspensoid agent by
Medicinal active ingredient and pharmaceutical grade auxiliary material composition, the medicinal active ingredient is Lamotrigine 50-150 parts by weight, described medicinal
Grade auxiliary material is by the filler of 50-800 parts by weight, the suspending agent of 10-50 parts by weight, the buffer of 10-50 parts by weight, 5-20 weight
The glidant composition of the sweetener of part, the flavouring agent of 1-10 parts by weight and 1-8 parts by weight.
It is highly preferred that invention further provides a kind of Lamotrigine dry suspensoid agent, the Lamotrigine dry suspensoid agent
It is made of medicinal active ingredient and pharmaceutical grade auxiliary material, the medicinal active ingredient is 100 parts by weight of Lamotrigine, the pharmaceutical grade
Auxiliary material is by the filler of 100-600 parts by weight, the suspending agent of 15-40 parts by weight, the buffer of 10-30 parts by weight, 5-10 weight
The glidant composition of the sweetener of part, the flavouring agent of 1-6 parts by weight and 1-5 parts by weight.
Wherein Lamotrigine be anhydrous lamotrigine, preferably 5 μm -150 μm of partial size D90.It is more preferable 10 μm -120 μm, optimal
30 μm -90 μm are selected, the D90 refers to that particle diameter accounts for 90% less than the particle of the partial size.
The selection of D90, applicant have found during screening test, when Lamotrigine is more than 150 μm, then be formulated as it is wet
When suspension, such as when taking dose is lower (such as 1ml), sampling can be uneven, when Lamotrigine is lower than 5 μm, prepares first
Dry suspensoid agent quality and selected 5 μm -150 μm of quality without marked difference, and prepare extremely difficult.Waste of manpower and wealth
Power does not have practicability.
Suspending agent in the present invention is xanthan gum, this is an important auxiliary material of the invention.With 100 parts by weight of Lamotrigine
Meter, xanthan gum dosage are 10-50 parts by weight, preferably 15-40 parts by weight, more preferable 18-25 parts by weight, in most preferred embodiment
In, in terms of 100 parts by weight of Lamotrigine, xanthan gum dosage is 20 parts by weight.
Inventor has carried out the research of liquid suspension first, is prepared for two kinds of Lamotrigine liquid suspensions, respectively
Prescription 20160304-1 and 20160323-2, specific prescription are shown in Table 1.
1 liquid suspension of table
Prescription 20160304-1,20160323-2 Lamotrigine liquid suspension preparation method provided by the invention include with
Lower step:
1, successively that the sodium dihydrogen phosphate-water of recipe quantity, polyethylene glycol, Sucralose, strawberry is fragrant under stirring
Essence, potassium sorbate and maltitol are added in the purified water of recipe quantity 80%, and agitating paddle speed is 300rpm to 500rpm.
2, after above-mentioned auxiliary material all dissolution, it is slowly added to the carragheen (addition is too fast, and carragheen can agglomerate) of recipe quantity,
During the addition process, as suspension viscosity increases, rotating speed of agitator is gradually increased, liquid is made to be always maintained at into vortex shape, to
After carragheen adds, continue stirring hydration 1 hour, rotating speed of agitator is 500rpm to 1100rpm.
3, after carragheen has been hydrated, it is gradually added into the Lamotrigine of recipe quantity, continues stirring 30 minutes after adding, bottling is
Can, rotating speed of agitator is 800rpm to 1100rpm.
Liquid Lamotrigine suspension is fitted into 250ml pharmaceutical grade PET plastic bottle, after sealing, is placed in 40 DEG C, RH75%
The stability that liquid suspension under acceleration environment is investigated in climatic chamber under the conditions of (relative humidity), the results are shown in Table 2.
2 Lamotrigine liquid suspension accelerated test of table
As shown in Table 2, prescription 20160323-2 (concentration 10mg/ml) is in accelerated test, and 40 DEG C, generate under RH75%
Impurity C is the prescription 20160304-1 (half of concentration 5mg/ml.Impurity C is the main degradation products of Lamotrigine, United States Pharmacopeia
The limitation of the impurity C of middle regulation Lamotrigine ordinary tablet is 0.50%, and the limitation of Lamotrigine bite-dispersion tablets impurity C is
0.30%, by accelerated test result it can be deduced that even if selecting concentration that can not reach under room temperature for 10mg/ml liquid suspension
The requirement of storage 2 years.
It has been reported that oxidation product of the Lamotrigine impurity C for generation during its storage, therefore the present invention also investigates
Influences of the different antioxidants to Lamotrigine liquid suspension stability.Carried out respectively cloves hydroxyanisole (BHA),
Dibutyl hydroxy toluene (BHT), propylgallate antioxidant to this preparation impurity C influence research, find 3 kinds of antioxygens
Agent does not all have obvious effects on the impurity C for inhibiting Lamotrigine liquid suspension to generate during storage.
The present invention also observes the physical stability of Lamotrigine liquid suspension under room temperature, and concrete outcome is shown in Fig. 1 and Fig. 2.
By microscope photograph it is found that Lamotrigine liquid suspension does not observe bulk crystals when just preparing, and put at normal temperature
After setting 3 days, there are a large amount of bulk crystals to occur, and as the time increases, crystal has the tendency that becoming larger.By document report it is found that
This bulk crystals may be the hydrate that Lamotrigine is formed in water.Lamotrigine liquid suspension during storage can
Bulk crystals are generated, not only influence the appearance of liquid suspension, but also the crystal to agglomerate is not easy to scatter again, influences medication
The accuracy of dosage.
Since the physical stability and chemical stability of Lamotrigine liquid suspension are poor, and the technical problem is difficult to solve
Certainly.Applicant carried out the research and development of Lamotrigine dry suspensoid agent.However it there are no the listing of Lamotrigine dry suspensoid agent both at home and abroad
And report, therefore applicant needs to carry out a series of screening for Lamotrigine dry suspensoid agent pharmaceutical adjunct.
It has especially carried out the screening of suspending agent: having screened xanthan gum, carragheen, sodium carboxymethylcellulose, hydroxypropyl respectively
The screening of methylcellulose K4M, carbomer940.
The screening of 3 suspending agent of table
By suspension jitter time test evaluated, (be added equivalent amount of water after, prepare wet mixing suspension shaking dispersion when
Between, short be preferred with the time) and sedimentation volume ratio (2015 editions regulation sedimentation volume ratios of Chinese Pharmacopoeia should be not less than 0.90) screen
Suspending agent.
4 testing result of table
Testing result is shown in Table 4, wherein selecting xanthan gum for most preferably suspending agent, advantage is that jitter time is fast, and suspension is heavy
It is high that volume ratio drops, and drug will not settle in use.
The present invention also investigates the dosage of xanthan gum.It is shown in Table 5
The screening of 5 xanthan gum dosage of table
6 testing result of table
Inspection result is shown in Table, and final choice xanthan gum is 20 parts by weight, because after increasing prescription xanthan gum dosage, when dispersion
Between obviously increase, jitter time variation is little after reducing prescription xanthan gum dosage, it is contemplated that the xanthan gluing of producer's different batches
Degree can be variant, if certain batch viscosity of xanthan gums is less than normal, the prescription viscosity of low dosage xanthan gum also can be less than normal, prescription settling volume
Product quality is influenced than 0.90 may be lower than, and when xanthan gum dosage is greater than 100 parts by weight, the Lamotrigine solution
When configuration, viscosity be will increase, and jitter time can excessively be grown, and be not easy to disperse, therefore the dosage of the xanthan gum, be in Lamotrigine
Under conditions of 100 parts by weight, no more than 100 parts by weight, and under this condition, xanthan gum preferably 20 parts by weight.
The present invention provides a kind of prescriptions of Lamotrigine dry suspensoid agent, are shown in Table 7
7 Lamotrigine dry suspensoid agent formula of table
The present invention also provides the wet granulation methods of 20160810-1:
1, all auxiliary materials in Lamotrigine bulk pharmaceutical chemicals and prescription are crossed to 1016 microns of sieve respectively；
2, the Lamotrigine bulk pharmaceutical chemicals of recipe quantity are weighed and interior mix 5 in the wet granulator of suitable volumes to auxiliary material
After minute, suitable quantity of water is added to pelletize.Wet granulator stirring shear velocity is 300-500rpm, and Granulation time is 3-5 minutes；
3, it with after 6350 microns of the wet whole grain of sieve, is dried under the conditions of 50 DEG C to LOD < 2% with fluidized bed.LOD is system
The water-content indicator of grain, when reaching LOD < 2%, it is believed that the moisture in wet granulation has been removed；
4, whole grain is done with 1016um sieve, and with the export-oriented auxiliary material of recipe quantity as in the mixed instrument of suitable volumes, with 20
Rev/min speed mix 10 minutes；
5, the Lamotrigine dry suspensoid agent prepared is packed using automatic packaging machine.
Prescription 20160815-1 is identical as supplementary product kind used in prescription 20160810-1 and dosage, and preparation process uses dry powder
Mixing.It is shown in Table 8.
Table 8
Prescription 20160815-1 Lamotrigine dry suspensoid agent preparation method provided by the invention the following steps are included:
1, all auxiliary materials in Lamotrigine bulk pharmaceutical chemicals and prescription are crossed to 1016 microns of sieve respectively；
2, the Lamotrigine bulk pharmaceutical chemicals and all auxiliary materials for weighing recipe quantity, are placed in the mixed instrument being sized for, with 20-
50 revs/min of speed mixes 10-20 minutes；
3, the Lamotrigine dry suspensoid agent prepared is packed using automatic packaging machine.
Prescription 20160815-1 Lamotrigine dry suspensoid agent indices are (when such as content, uniformity of dosage units, loading amount, dispersion
Between, dissolution) detection is qualified, using dry powder blend, simple process.
All auxiliary materials must cross 1016 microns of sieve mesh: some auxiliary materials can agglomerate (such as air during storage
Caused by humidity water suction), the purpose for crossing sieve is to be broken up, and be uniformly mixed convenient for subsequent.
Xanthan gum is not contained in prescription 20160822-1 Lamotrigine dry suspensoid agent, is specifically shown in Table 9.Design the mesh of this prescription
Be effect for studying xanthan gum in terms of inhibiting Lamotrigine gas hydrate synthesis.The process flow of prescription 20160822-1
It is identical as prescription 20160815-1.
Table 9
Prescription 20160815-1 and 20160822-1 dry suspensoid agent are suspended with the liquid that water is prepared into 10mg/ml respectively
Agent, and sampled respectively at 2,4,8 and 24 hours, after centrifugation, the obtained suspension solute sample powder in liquid suspension.
Then powder x-ray diffraction experiment is carried out to Lamotrigine bulk pharmaceutical chemicals and obtained sample.Concrete outcome is shown in X-ray diffractogram
Spectrogram 3 arrives Fig. 6.
From powder x-ray diffraction result, we have found that in prescription 20160815-1 Lamotrigine 2,4,8,24 hours with
Lamotrigine bulk pharmaceutical chemicals crystalline form having the same, and the Lamotrigine crystal form in the prescription 20160822-1 without xanthan gum is 8
It begins to change after hour.By United States Patent (USP) US7390807B2 and US8486927B2 it is found that the crystal form newly formed is Rameau three
The hydrate of piperazine.
The above results make us surprised, because it has generally been thought that Lamotrigine anhydride one, which contacts water, will initially form hydration
Object.Also document report Lamotrigine is readily formed hydrate in aqueous solution.But it present invention discover that is helped using a small amount of
Suspension (being xanthan gum in the present invention), plays the role of inhibiting Lamotrigine gas hydrate synthesis.
Lamotrigine hydrate has different crystal forms, and after xanthan gum is added, i.e., 20160815-1 prescription is configured to
After liquid suspension, in 24 hours, the speed for forming Lamotrigine hydrate can be significantly reduced, and showing as transformation of crystal can become
Slowly.This is of great significance in quality stability when patient is configured to liquid suspension using dry suspensoid agent, ensure that dry
It is more stable compared to when xanthan gum is not added that suspension is configured to liquid suspension quality in 24 hours.
The present invention further provides a kind of Lamotrigine dry suspensoid agent, the filler be sucrose, mannitol, lactose one
Kind or multiple combinations.
Preferably sucrose, the reason is that, it both can be used as sweetener and be also used as filler, filler loading is big, selects sugarcane
Sugar is because of its safety, using wide.
Particle diameter of sucrose D90 is 50 μm -400 μm, preferably 50 μm -300 μm, more preferable 50 μm -180 μm.The reason is that sucrose is
Filler in prescription, the dosage in prescription is big (about 80%), if partial size is too small, powder flowbility is poor, drug can be made to contain
Amount is uneven, and powder packaging difficulty can also increase, can (partial size is respectively less than 180 with other supplementary material partial sizes if partial size is too big
μm) difference is too big, also result in that medicament contg is uneven, therefore the partial size of sucrose should control within the scope of one.Advantage is
Particle diameter of sucrose D90 is selected as 50 μm -180 μm, can both make drug mixing more evenly, can also improve the mobility of powder, just
In powder packaging.
The present invention further provides a kind of Lamotrigine dry suspensoid agent, the buffer is sodium citrate, citric acid, phosphoric acid
One or more combinations of sodium dihydrogen, disodium hydrogen phosphate；The flavouring agent is strawberry flavor, banana flavor, sweet orange taste, mint flavored essence
One of；The sweetener is one or more kinds of combinations of sucrose, Sucralose, Aspartame, saccharin sodium.
The buffer should have enough buffer capacities, be maintained at suspension pH within the scope of required pH, preferably phosphoric acid
Disodium hydrogen.The preferred 5-6. of pH
The preferred sweet orange taste essence of the present invention.
The present invention further provides a kind of Lamotrigine dry suspensoid agent, the glidant is silica, magnesium stearate, cunning
Mountain flour, sodium stearyl fumarate one of.
The present invention provides the preparation methods of Lamotrigine dry suspensoid agent, the preparation method is that dry powder blend, wet process system
One kind of grain, dry granulation.
Dry powder blend simple process, favorable reproducibility.
Lamotrigine dry suspensoid agent can wrap in pharmaceutical grade plastic bottle or vial for being used for multiple times, and also can wrap
For being intended for single use in pouch.
Lamotrigine dry suspensoid agent can be by pharmacists or patient parent or other adults wanting to specifications
It asks and is configured to certain concentration with water, the preferably liquid suspension of 10mg/ml is oral for patient.According to patient body weight on specification
Patient is calculated with the table of medication magnitude relation this time to take medicine volume, is inhaled by using matched 1ml 10ml oral syringe
It takes in the mouth of suspension direct injection patient Yu of exact volume.
Innovative point of the invention:
Lamotrigine dry suspensoid agent in the present invention is compared its tablet, can be suspended in water with Quick uniform, improve medicine
Object mouthfeel is taken more simply, and dosage is more acurrate；Compared to liquid suspension (liquid suspension is also wet mixing suspension), have
Better chemical stability, only minimal amount of impurity generates before the deadline.In addition, suspending agent xanthan gum in the present invention, no
Only suspending effect is good, and jitter time is fast, and when being configured as Lamotrigine liquid suspension, transformation of crystal is significantly slack-off, suppression
The formation of Lamotrigine hydrate processed, liquid suspension physical stability is more preferable, these advantages make Lamotrigine in the present invention
Dry suspensoid agent has good patient dependence.
Detailed description of the invention
Fig. 1 prescription 20160304-1 has just prepared photo under rear microscope (100 times of amplification)；
Photo under microscope (100 times of amplification) after being placed 3 days after Fig. 2 prescription 20160304-1 preparation；
Fig. 3 Lamotrigine active constituent, powder x-ray diffraction of the prescription 20160815-1 and 20160822-1 at 2 hours
Figure (ordinate is intensity counting, and abscissa is 2 angles θ, and API is bulk pharmaceutical chemicals)；
Fig. 4 Lamotrigine active constituent, powder x-ray diffraction of the prescription 20160815-1 and 20160822-1 at 4 hours
Figure (ordinate is intensity counting, and abscissa is 2 angles θ, and API is bulk pharmaceutical chemicals)；
Fig. 5 Lamotrigine active constituent, powder x-ray diffraction of the prescription 20160815-1 and 20160822-1 at 8 hours
Figure (ordinate is intensity counting, and abscissa is 2 angles θ, and API is bulk pharmaceutical chemicals)；
Fig. 6 Lamotrigine active constituent, powder x-ray diffraction of the prescription 20160815-1 and 20160822-1 at 24 hours
Figure (ordinate is intensity counting, and abscissa is 2 angles θ, and API is bulk pharmaceutical chemicals).
Specific embodiment
The following examples are only used for further illustrating the present invention but are not limited to the present invention.It is all to be based on above content of the present invention
The technology realized belongs to the scope of the invention.
Embodiment 1
Prescription 1
Dry powder blend, specific steps are as follows:
1, all auxiliary materials in Lamotrigine bulk pharmaceutical chemicals and prescription are crossed to 1016 microns of sieve respectively.
2, the Lamotrigine bulk pharmaceutical chemicals and all auxiliary materials for weighing recipe quantity, are placed in the mixed instrument being sized for, with 20
Rev/min speed mix 10 minutes.
3, the Lamotrigine dry suspensoid agent prepared is packed using automatic packaging machine.It is dry to obtain the Lamotrigine
Suspension.
Embodiment 2
Using the prescription 1 of embodiment 1, wet granulation is used.
Specific steps are as follows:
1, all auxiliary materials in Lamotrigine bulk pharmaceutical chemicals and prescription are crossed to 1016 microns of sieve respectively.
2, the Lamotrigine bulk pharmaceutical chemicals of recipe quantity are weighed and interior mix 5 in the wet granulator of suitable volumes to auxiliary material
After minute, suitable quantity of water is added to pelletize.Wet granulator stirring shear velocity is 300rpm, and Granulation time is 5 minutes.
3, it with after 6350 microns of the wet whole grain of sieve, is dried under the conditions of 50 DEG C to LOD < 2% with fluidized bed.
4, whole grain is done with 1016um sieve, and with the export-oriented auxiliary material of recipe quantity as in the mixed instrument of suitable volumes, with 20
Rev/min speed mix 10 minutes.
5, the Lamotrigine dry suspensoid agent prepared is packed using automatic packaging machine.It is dry to obtain the Lamotrigine
Suspension.
Embodiment 3
Prescription 2
It is prepared using 1 dry powder blend method of embodiment.
Embodiment 4
Prescription is the prescription 2 of embodiment 3, and preparation method is the wet granulation of embodiment 2.
Embodiment 5
Prescription 3
It is prepared using 1 dry powder blend method of embodiment.
Embodiment 6
Prescription is the prescription 3 of embodiment 5, and preparation method is the wet granulation of embodiment 2.
Embodiment 7
Prescription 4
It is prepared using 1 dry powder blend method of embodiment.
Embodiment 8
Prescription is the prescription 4 of embodiment 7, and preparation method is the wet granulation of embodiment 2.
Embodiment 9
Prescription 5
It is prepared using 1 dry powder blend method of embodiment.
Embodiment 10
Prescription 6
Preparation method is identical as 1 method of embodiment
Embodiment 11
Prescription is identical as other auxiliary materials of prescription 1 in embodiment 1, Lamotrigine 30mg
Preparation method is identical as 1 method of embodiment.
Embodiment 12
Prescription is identical as other supplementary materials of prescription 5 in embodiment 9, xanthan gum 10mg
Preparation method is identical as 9 method of embodiment.
Embodiment 13
Prescription is identical as other supplementary materials of prescription 5 in embodiment 9, xanthan gum 15mg
Preparation method is identical as 9 method of embodiment.
Embodiment 14
Prescription is identical as other supplementary materials of prescription 5 in embodiment 9, xanthan gum 18mg
Preparation method is identical as 9 method of embodiment.
Embodiment 15
Prescription is identical as other supplementary materials of prescription 5 in embodiment 9, xanthan gum 20mg
Preparation method is identical as 9 method of embodiment.
Embodiment 16
Prescription is identical as other supplementary materials of prescription 5 in embodiment 9, xanthan gum 50mg
Preparation method is identical as 9 method of embodiment.
Suspending agent in the present invention is xanthan gum, this is an important auxiliary material of the invention.With 100 parts by weight of Lamotrigine
Meter, xanthan gum dosage are 10-50 parts by weight, and preferably 15-40 parts by weight, more preferable 18-25 parts by weight are commented according to technical effect
Estimate, most preferred embodiment is, in terms of 100 parts by weight of Lamotrigine, xanthan gum dosage is 20 parts by weight.
Wherein Lamotrigine be anhydrous lamotrigine, preferably 5 μm -150 μm of partial size D90.It is more preferable 10 μm -120 μm, optimal
30 μm -90 μm are selected, the D90 refers to that particle diameter accounts for 90% less than the particle of the partial size.
Particle diameter of sucrose D90 is 50 μm -400 μm, preferably 50 μm -300 μm, more preferable 50 μm -180 μm.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
Limitations on the scope of the patent of the present invention therefore cannot be interpreted as, it is noted that for those skilled in the art,
Without departing from the inventive concept of the premise, several deformations and transformation can also be made, these belong to protection model of the invention
It encloses, therefore, the scope of protection of the patent of the present invention is determined by the appended claims.
Claims (5)
1. a kind of Lamotrigine dry suspensoid agent, which is characterized in that the Lamotrigine dry suspensoid agent is by medicinal active ingredient and medicine
It is formed with grade auxiliary material, the medicinal active ingredient is Lamotrigine 50-150 parts by weight；The pharmaceutical grade auxiliary material is by 50-800 weight
Measure the filler of part, the suspending agent of 10-50 parts by weight, the buffer of 10-50 parts by weight, 5-20 parts by weight sweetener, 1-10
The flavouring agent of parts by weight and the glidant composition of 1-8 parts by weight, the filler is one kind or more of sucrose, mannitol, lactose
Kind combination；The buffer is one or more combinations of sodium citrate, citric acid, sodium dihydrogen phosphate, disodium hydrogen phosphate；It is described
Glidant be silica, magnesium stearate, talcum powder, sodium stearyl fumarate one of；The suspending agent is xanthan gum.
2. Lamotrigine dry suspensoid agent according to claim 1, which is characterized in that the Lamotrigine dry suspensoid agent is by medicine
It is formed with active constituent and pharmaceutical grade auxiliary material, the medicinal active ingredient is 100 parts by weight of Lamotrigine, the pharmaceutical grade auxiliary material
By the filler of 100-600 parts by weight, the suspending agent of 15-40 parts by weight, the buffer of 10-30 parts by weight, 5-10 parts by weight
The glidant of sweetener, the flavouring agent of 1-6 parts by weight and 1-5 parts by weight forms.
3. Lamotrigine dry suspensoid agent according to claim 1, which is characterized in that the partial size D90 of the Lamotrigine is 5
μm -150 μm, the D90 refers to that particle diameter is less than the particle of the partial size and accounts for 90%.
4. Lamotrigine dry suspensoid agent according to claim 1, which is characterized in that the sweetener is sucrose, trichlorine sugarcane
One or more kinds of combinations of sugar, Aspartame, saccharin sodium.
5. a kind of preparation method of Lamotrigine dry suspensoid agent described in claim 1, which is characterized in that the preparation method is that
One kind of dry powder blend, wet granulation or dry granulation.
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| CN109864971B (en) * | 2019-04-08 | 2021-12-17 | 西安远大德天药业股份有限公司 | Granules of lamotrigine solid dispersion and preparation method thereof |
| CN113214177B (en) * | 2021-04-16 | 2022-05-03 | 上海奥科达生物医药科技有限公司 | Crystal form of lamotrigine hydrate, preparation method thereof and composition containing crystal form |
| CN114432241B (en) * | 2021-12-21 | 2023-07-14 | 上海奥全生物医药科技有限公司 | Rapidly-dispersed suspension composition, preparation method and application thereof |
| CN115068422B (en) * | 2022-08-19 | 2022-11-29 | 上海奥科达生物医药科技有限公司 | Lamotrigine wet suspension and preparation method and application thereof |
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